TY  - JOUR
AU  - Krunić, Matija
AU  - Ristić, Biljana
AU  - Bošnjak, Mihajlo
AU  - Paunović, Verica
AU  - Tovilović-Kovačević, Gordana
AU  - Zogović, Nevena
AU  - Mirčić, Aleksandar
AU  - Marković, Zoran
AU  - Todorović-Marković, Biljana
AU  - Jovanović, Svetlana P.
AU  - Kleut, Duška
AU  - Mojović, Miloš
AU  - Nakarada, Đura
AU  - Marković, Olivera
AU  - Vuković, Irena
AU  - Harhaji-Trajković, Ljubica
AU  - Trajković, Vladimir S.
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9980
AB  - We investigated the ability of graphene quantum dot (GQD) nanoparticles to protect SH-SY5Y human neuroblastoma cells from oxidative/nitrosative stress induced by iron-nitrosyl complex sodium nitroprusside (SNP).GQD reduced SNP cytotoxicity by preventing mitochondrial depolarization, caspase-2 activation, and subsequent apoptotic death. Although GQD diminished the levels of nitric oxide (NO) in SNP-exposed cells, NO scavengers displayed only a slight protective effect, suggesting that NO quenching was not the main protective mechanism of GQD. GQD also reduced SNP-triggered increase in the intracellular levels of hydroxyl radical (•OH), superoxide anion (O2•- ), and lipid peroxidation. Nonselective antioxidants, •OH scavenging, and iron chelators, but not superoxide dismutase, mimicked GQD cytoprotective activity, indicating that GQD protect cells by neutralizing •OH generated in the presence of SNP-released iron. Cellular internalization of GQD was required for optimal protection, since a removal of extracellular GQD by extensive washing only partly diminished their protective effect. Moreover, GQD cooperated with SNP to induce autophagy, as confirmed by the inhibition of autophagylimiting Akt/PRAS40/mTOR signaling and increase in autophagy gene transcription, protein levels of proautophagic beclin-1 and LC3-II, formation of autophagic vesicles, and degradation of autophagic target p62. The antioxidant activity of GQD was not involved in autophagy induction, as antioxidants N-acetylcysteine and dimethyl sulfoxide failed to stimulate autophagy in SNP-exposed cells. Pharmacological inhibitors of early (wortmannin, 3-methyladenine) or late stages of autophagy (NH4Cl) efficiently reduced the protective effect of GQD. Therefore, the ability of GQD to prevent the in vitro neurotoxicity of SNP depends on both •OH/NO scavenging and induction of cytoprotective autophagy.
T2  - Free Radical Biology and Medicine
T1  - Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death
VL  - 177
SP  - 167
EP  - 180
DO  - 10.1016/j.freeradbiomed.2021.10.025
ER  - 

@article{
author = "Krunić, Matija and Ristić, Biljana and Bošnjak, Mihajlo and Paunović, Verica and Tovilović-Kovačević, Gordana and Zogović, Nevena and Mirčić, Aleksandar and Marković, Zoran and Todorović-Marković, Biljana and Jovanović, Svetlana P. and Kleut, Duška and Mojović, Miloš and Nakarada, Đura and Marković, Olivera and Vuković, Irena and Harhaji-Trajković, Ljubica and Trajković, Vladimir S.",
year = "2021",
abstract = "We investigated the ability of graphene quantum dot (GQD) nanoparticles to protect SH-SY5Y human neuroblastoma cells from oxidative/nitrosative stress induced by iron-nitrosyl complex sodium nitroprusside (SNP).GQD reduced SNP cytotoxicity by preventing mitochondrial depolarization, caspase-2 activation, and subsequent apoptotic death. Although GQD diminished the levels of nitric oxide (NO) in SNP-exposed cells, NO scavengers displayed only a slight protective effect, suggesting that NO quenching was not the main protective mechanism of GQD. GQD also reduced SNP-triggered increase in the intracellular levels of hydroxyl radical (•OH), superoxide anion (O2•- ), and lipid peroxidation. Nonselective antioxidants, •OH scavenging, and iron chelators, but not superoxide dismutase, mimicked GQD cytoprotective activity, indicating that GQD protect cells by neutralizing •OH generated in the presence of SNP-released iron. Cellular internalization of GQD was required for optimal protection, since a removal of extracellular GQD by extensive washing only partly diminished their protective effect. Moreover, GQD cooperated with SNP to induce autophagy, as confirmed by the inhibition of autophagylimiting Akt/PRAS40/mTOR signaling and increase in autophagy gene transcription, protein levels of proautophagic beclin-1 and LC3-II, formation of autophagic vesicles, and degradation of autophagic target p62. The antioxidant activity of GQD was not involved in autophagy induction, as antioxidants N-acetylcysteine and dimethyl sulfoxide failed to stimulate autophagy in SNP-exposed cells. Pharmacological inhibitors of early (wortmannin, 3-methyladenine) or late stages of autophagy (NH4Cl) efficiently reduced the protective effect of GQD. Therefore, the ability of GQD to prevent the in vitro neurotoxicity of SNP depends on both •OH/NO scavenging and induction of cytoprotective autophagy.",
journal = "Free Radical Biology and Medicine",
title = "Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death",
volume = "177",
pages = "167-180",
doi = "10.1016/j.freeradbiomed.2021.10.025"
}

Krunić, M., Ristić, B., Bošnjak, M., Paunović, V., Tovilović-Kovačević, G., Zogović, N., Mirčić, A., Marković, Z., Todorović-Marković, B., Jovanović, S. P., Kleut, D., Mojović, M., Nakarada, Đ., Marković, O., Vuković, I., Harhaji-Trajković, L.,& Trajković, V. S.. (2021). Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death. in Free Radical Biology and Medicine, 177, 167-180.
https://doi.org/10.1016/j.freeradbiomed.2021.10.025

Krunić M, Ristić B, Bošnjak M, Paunović V, Tovilović-Kovačević G, Zogović N, Mirčić A, Marković Z, Todorović-Marković B, Jovanović SP, Kleut D, Mojović M, Nakarada Đ, Marković O, Vuković I, Harhaji-Trajković L, Trajković VS. Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death. in Free Radical Biology and Medicine. 2021;177:167-180.
doi:10.1016/j.freeradbiomed.2021.10.025 .

Krunić, Matija, Ristić, Biljana, Bošnjak, Mihajlo, Paunović, Verica, Tovilović-Kovačević, Gordana, Zogović, Nevena, Mirčić, Aleksandar, Marković, Zoran, Todorović-Marković, Biljana, Jovanović, Svetlana P., Kleut, Duška, Mojović, Miloš, Nakarada, Đura, Marković, Olivera, Vuković, Irena, Harhaji-Trajković, Ljubica, Trajković, Vladimir S., "Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death" in Free Radical Biology and Medicine, 177 (2021):167-180,
https://doi.org/10.1016/j.freeradbiomed.2021.10.025 . .

TY  - CONF
AU  - Kravić-Stevović, Tamara K.
AU  - Martinović, Tamara
AU  - Ćirić, Darko
AU  - Paunović, Verica G.
AU  - Ristić, Biljana
AU  - Marković, Zoran M.
AU  - Todorović-Marković, Biljana
AU  - Kosić, Milica
AU  - Prekodravac, Jovana
AU  - Micusik, Matej
AU  - Spitalsky, Zdeno
AU  - Trajković, Vladimir S.
AU  - Harhaji-Trajković, Ljubica M.
AU  - Bumbaširević, Vladimir Ž.
PY  - 2018
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8740
PB  - Belgrade : Serbian Academy of Sciences and Arts
C3  - Program and Book of Abstracts / First International Conference on Electron Microscopy of Nanostructures ELMINA 2018, August 27-29, 2018, Belgrade, Serbia
T1  - Transmission Electron Microscopy in Evaluation of Curcumin Nanoparticles Cellular Uptake
SP  - 266
EP  - 268
UR  - https://hdl.handle.net/21.15107/rcub_vinar_8740
ER  - 

@conference{
author = "Kravić-Stevović, Tamara K. and Martinović, Tamara and Ćirić, Darko and Paunović, Verica G. and Ristić, Biljana and Marković, Zoran M. and Todorović-Marković, Biljana and Kosić, Milica and Prekodravac, Jovana and Micusik, Matej and Spitalsky, Zdeno and Trajković, Vladimir S. and Harhaji-Trajković, Ljubica M. and Bumbaširević, Vladimir Ž.",
year = "2018",
publisher = "Belgrade : Serbian Academy of Sciences and Arts",
journal = "Program and Book of Abstracts / First International Conference on Electron Microscopy of Nanostructures ELMINA 2018, August 27-29, 2018, Belgrade, Serbia",
title = "Transmission Electron Microscopy in Evaluation of Curcumin Nanoparticles Cellular Uptake",
pages = "266-268",
url = "https://hdl.handle.net/21.15107/rcub_vinar_8740"
}

Kravić-Stevović, T. K., Martinović, T., Ćirić, D., Paunović, V. G., Ristić, B., Marković, Z. M., Todorović-Marković, B., Kosić, M., Prekodravac, J., Micusik, M., Spitalsky, Z., Trajković, V. S., Harhaji-Trajković, L. M.,& Bumbaširević, V. Ž.. (2018). Transmission Electron Microscopy in Evaluation of Curcumin Nanoparticles Cellular Uptake. in Program and Book of Abstracts / First International Conference on Electron Microscopy of Nanostructures ELMINA 2018, August 27-29, 2018, Belgrade, Serbia
Belgrade : Serbian Academy of Sciences and Arts., 266-268.
https://hdl.handle.net/21.15107/rcub_vinar_8740

Kravić-Stevović TK, Martinović T, Ćirić D, Paunović VG, Ristić B, Marković ZM, Todorović-Marković B, Kosić M, Prekodravac J, Micusik M, Spitalsky Z, Trajković VS, Harhaji-Trajković LM, Bumbaširević VŽ. Transmission Electron Microscopy in Evaluation of Curcumin Nanoparticles Cellular Uptake. in Program and Book of Abstracts / First International Conference on Electron Microscopy of Nanostructures ELMINA 2018, August 27-29, 2018, Belgrade, Serbia. 2018;:266-268.
https://hdl.handle.net/21.15107/rcub_vinar_8740 .

Kravić-Stevović, Tamara K., Martinović, Tamara, Ćirić, Darko, Paunović, Verica G., Ristić, Biljana, Marković, Zoran M., Todorović-Marković, Biljana, Kosić, Milica, Prekodravac, Jovana, Micusik, Matej, Spitalsky, Zdeno, Trajković, Vladimir S., Harhaji-Trajković, Ljubica M., Bumbaširević, Vladimir Ž., "Transmission Electron Microscopy in Evaluation of Curcumin Nanoparticles Cellular Uptake" in Program and Book of Abstracts / First International Conference on Electron Microscopy of Nanostructures ELMINA 2018, August 27-29, 2018, Belgrade, Serbia (2018):266-268,
https://hdl.handle.net/21.15107/rcub_vinar_8740 .

TY  - JOUR
AU  - Paunović, Verica G.
AU  - Ristić, Biljana
AU  - Marković, Zoran M.
AU  - Todorović-Marković, Biljana
AU  - Kosić, Milica
AU  - Prekodravac, Jovana
AU  - Kravić-Stevović, Tamara K.
AU  - Martinović, Tamara
AU  - Mičušik, Matej
AU  - Špitalsky, Zdenko
AU  - Trajković, Vladimir S.
AU  - Harhaji-Trajković, Ljubica M.
PY  - 2016
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1084
AB  - Indian spice curcumin is known for its anticancer properties, but the anticancer mechanisms of nanoparticulate curcumin have not been completely elucidated. We here investigated the in vitro anticancer effect of blue light (470 nm, 1 W)-irradiated curcumin nanoparticles prepared by tetrahydrofuran/water solvent exchange, using U251 glioma, B16 melanoma, and H460 lung cancer cells as targets. The size of curcumin nanocrystals was approximately 250 nm, while photoexcitation induced their oxidation and partial agglomeration. Although cell membrane in the absence of light was almost impermeable to curcumin nanoparticles, photoexcitation stimulated their internalization. While irradiation with blue light (1-8 min) or nanocurcumin (1.25-10 mu g/ml) alone was only marginally toxic to tumor cells, photoexcited nanocurcumin displayed a significant cytotoxicity depending both on the irradiation time and nanocurcumin concentration. Photoexcited nanocurcumin induced phosphorylation of cJun N-terminal kinase (JNK), mitochondrial depolarization, caspase-3 activation, and cleavage of poly (ADP-ribose) polymerase, indicating apoptotic cell death. Accordingly, pharmacologial inhibition of JNK and caspase activity rescued cancer cells from photoexcited nanocurcumin. On the other hand, antioxidant treatment did not reduce photocytotoxicity of nanocurcumin, arguing against the involvement of oxidative stress. By demonstrating the ability of photoexcited nanocurcumin to induce oxidative-stress independent, JNK-and caspase-dependent apoptosis, our results support its further investigation in cancer therapy.
PB  - Springer
T2  - Biomedical Microdevices
T1  - c-Jun N-terminal kinase-dependent apoptotic photocytotoxicity of solvent exchange-prepared curcumin nanoparticles
VL  - 18
IS  - 2
DO  - 10.1007/s10544-016-0062-2
ER  - 

@article{
author = "Paunović, Verica G. and Ristić, Biljana and Marković, Zoran M. and Todorović-Marković, Biljana and Kosić, Milica and Prekodravac, Jovana and Kravić-Stevović, Tamara K. and Martinović, Tamara and Mičušik, Matej and Špitalsky, Zdenko and Trajković, Vladimir S. and Harhaji-Trajković, Ljubica M.",
year = "2016",
abstract = "Indian spice curcumin is known for its anticancer properties, but the anticancer mechanisms of nanoparticulate curcumin have not been completely elucidated. We here investigated the in vitro anticancer effect of blue light (470 nm, 1 W)-irradiated curcumin nanoparticles prepared by tetrahydrofuran/water solvent exchange, using U251 glioma, B16 melanoma, and H460 lung cancer cells as targets. The size of curcumin nanocrystals was approximately 250 nm, while photoexcitation induced their oxidation and partial agglomeration. Although cell membrane in the absence of light was almost impermeable to curcumin nanoparticles, photoexcitation stimulated their internalization. While irradiation with blue light (1-8 min) or nanocurcumin (1.25-10 mu g/ml) alone was only marginally toxic to tumor cells, photoexcited nanocurcumin displayed a significant cytotoxicity depending both on the irradiation time and nanocurcumin concentration. Photoexcited nanocurcumin induced phosphorylation of cJun N-terminal kinase (JNK), mitochondrial depolarization, caspase-3 activation, and cleavage of poly (ADP-ribose) polymerase, indicating apoptotic cell death. Accordingly, pharmacologial inhibition of JNK and caspase activity rescued cancer cells from photoexcited nanocurcumin. On the other hand, antioxidant treatment did not reduce photocytotoxicity of nanocurcumin, arguing against the involvement of oxidative stress. By demonstrating the ability of photoexcited nanocurcumin to induce oxidative-stress independent, JNK-and caspase-dependent apoptosis, our results support its further investigation in cancer therapy.",
publisher = "Springer",
journal = "Biomedical Microdevices",
title = "c-Jun N-terminal kinase-dependent apoptotic photocytotoxicity of solvent exchange-prepared curcumin nanoparticles",
volume = "18",
number = "2",
doi = "10.1007/s10544-016-0062-2"
}

Paunović, V. G., Ristić, B., Marković, Z. M., Todorović-Marković, B., Kosić, M., Prekodravac, J., Kravić-Stevović, T. K., Martinović, T., Mičušik, M., Špitalsky, Z., Trajković, V. S.,& Harhaji-Trajković, L. M.. (2016). c-Jun N-terminal kinase-dependent apoptotic photocytotoxicity of solvent exchange-prepared curcumin nanoparticles. in Biomedical Microdevices
Springer., 18(2).
https://doi.org/10.1007/s10544-016-0062-2

Paunović VG, Ristić B, Marković ZM, Todorović-Marković B, Kosić M, Prekodravac J, Kravić-Stevović TK, Martinović T, Mičušik M, Špitalsky Z, Trajković VS, Harhaji-Trajković LM. c-Jun N-terminal kinase-dependent apoptotic photocytotoxicity of solvent exchange-prepared curcumin nanoparticles. in Biomedical Microdevices. 2016;18(2).
doi:10.1007/s10544-016-0062-2 .

Paunović, Verica G., Ristić, Biljana, Marković, Zoran M., Todorović-Marković, Biljana, Kosić, Milica, Prekodravac, Jovana, Kravić-Stevović, Tamara K., Martinović, Tamara, Mičušik, Matej, Špitalsky, Zdenko, Trajković, Vladimir S., Harhaji-Trajković, Ljubica M., "c-Jun N-terminal kinase-dependent apoptotic photocytotoxicity of solvent exchange-prepared curcumin nanoparticles" in Biomedical Microdevices, 18, no. 2 (2016),
https://doi.org/10.1007/s10544-016-0062-2 . .

TY  - JOUR
AU  - Marković, Zoran M.
AU  - Ristić, Biljana Z.
AU  - Arsikin, Katarina M.
AU  - Klisic, Djordje G.
AU  - Harhaji-Trajković, Ljubica M.
AU  - Todorović-Marković, Biljana
AU  - Kepić, Dejan P.
AU  - Kravić-Stevović, Tamara K.
AU  - Jovanović, Svetlana P.
AU  - Milenković, Marina
AU  - Milivojević, Dušan
AU  - Bumbaširević, Vladimir Ž.
AU  - Dramićanin, Miroslav
AU  - Trajković, Vladimir S.
PY  - 2012
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/5025
AB  - The excellent photoluminescent properties of graphene quantum dots (GQD) makes them suitable candidates for biomedical applications, but their cytotoxicity has not been extensively studied. Here we show that electrochemically produced GQD irradiated with blue light (470 nm, 1 W) generate reactive oxygen species, including singlet oxygen, and kill U251 human glioma cells by causing oxidative stress. The cell death induced by photoexcited GQD displayed morphological and/or biochemical characteristics of both apoptosis (phosphatidylserine externalization, caspase activation. DNA fragmentation) and autophagy (formation of autophagic vesicles, LC3-I/LC3-II conversion, degradation of autophagic target p62). Moreover, a genetic inactivation of autophagy-essential LOB protein partly abrogated the photodynamic cytotoxicity of GQD. These data indicate potential usefulness of GQD in photodynamic therapy, but also raise concerns about their possible toxicity. (C) 2012 Elsevier Ltd. All rights reserved.
T2  - Biomaterials
T1  - Graphene quantum dots as autophagy-inducing photodynamic agents
VL  - 33
IS  - 29
SP  - 7084
EP  - 7092
DO  - 10.1016/j.biomaterials.2012.06.060
ER  - 

@article{
author = "Marković, Zoran M. and Ristić, Biljana Z. and Arsikin, Katarina M. and Klisic, Djordje G. and Harhaji-Trajković, Ljubica M. and Todorović-Marković, Biljana and Kepić, Dejan P. and Kravić-Stevović, Tamara K. and Jovanović, Svetlana P. and Milenković, Marina and Milivojević, Dušan and Bumbaširević, Vladimir Ž. and Dramićanin, Miroslav and Trajković, Vladimir S.",
year = "2012",
abstract = "The excellent photoluminescent properties of graphene quantum dots (GQD) makes them suitable candidates for biomedical applications, but their cytotoxicity has not been extensively studied. Here we show that electrochemically produced GQD irradiated with blue light (470 nm, 1 W) generate reactive oxygen species, including singlet oxygen, and kill U251 human glioma cells by causing oxidative stress. The cell death induced by photoexcited GQD displayed morphological and/or biochemical characteristics of both apoptosis (phosphatidylserine externalization, caspase activation. DNA fragmentation) and autophagy (formation of autophagic vesicles, LC3-I/LC3-II conversion, degradation of autophagic target p62). Moreover, a genetic inactivation of autophagy-essential LOB protein partly abrogated the photodynamic cytotoxicity of GQD. These data indicate potential usefulness of GQD in photodynamic therapy, but also raise concerns about their possible toxicity. (C) 2012 Elsevier Ltd. All rights reserved.",
journal = "Biomaterials",
title = "Graphene quantum dots as autophagy-inducing photodynamic agents",
volume = "33",
number = "29",
pages = "7084-7092",
doi = "10.1016/j.biomaterials.2012.06.060"
}

Marković, Z. M., Ristić, B. Z., Arsikin, K. M., Klisic, D. G., Harhaji-Trajković, L. M., Todorović-Marković, B., Kepić, D. P., Kravić-Stevović, T. K., Jovanović, S. P., Milenković, M., Milivojević, D., Bumbaširević, V. Ž., Dramićanin, M.,& Trajković, V. S.. (2012). Graphene quantum dots as autophagy-inducing photodynamic agents. in Biomaterials, 33(29), 7084-7092.
https://doi.org/10.1016/j.biomaterials.2012.06.060

Marković ZM, Ristić BZ, Arsikin KM, Klisic DG, Harhaji-Trajković LM, Todorović-Marković B, Kepić DP, Kravić-Stevović TK, Jovanović SP, Milenković M, Milivojević D, Bumbaširević VŽ, Dramićanin M, Trajković VS. Graphene quantum dots as autophagy-inducing photodynamic agents. in Biomaterials. 2012;33(29):7084-7092.
doi:10.1016/j.biomaterials.2012.06.060 .

Marković, Zoran M., Ristić, Biljana Z., Arsikin, Katarina M., Klisic, Djordje G., Harhaji-Trajković, Ljubica M., Todorović-Marković, Biljana, Kepić, Dejan P., Kravić-Stevović, Tamara K., Jovanović, Svetlana P., Milenković, Marina, Milivojević, Dušan, Bumbaširević, Vladimir Ž., Dramićanin, Miroslav, Trajković, Vladimir S., "Graphene quantum dots as autophagy-inducing photodynamic agents" in Biomaterials, 33, no. 29 (2012):7084-7092,
https://doi.org/10.1016/j.biomaterials.2012.06.060 . .

TY  - JOUR
AU  - Marković, Zoran M.
AU  - Harhaji-Trajković, Ljubica M.
AU  - Todorović-Marković, Biljana
AU  - Kepić, Dejan P.
AU  - Arsikin, Katarina M.
AU  - Jovanović, Svetlana P.
AU  - Pantovic, Aleksandar C.
AU  - Dramićanin, Miroslav
AU  - Trajković, Vladimir S.
PY  - 2011
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/4179
AB  - The present study compared the photothermal anticancer activity of near-infrared (NIR)-excited graphene nanoparticles and carbon nanotubes (CNT). Despite lower NIR-absorbing capacity, suspension of polyvinylpyrrolidone-coated graphene sheets exposed to NIR radiation (808 nm, 2 W/cm(2)) generated more heat than DNA or sodium dodecylbenzenesulfonate-solubilized single-wall CNT under the same conditions. Accordingly, graphene nanoparticles performed significantly better than CNT in inducing photothermal death of U251 human glioma cells in vitro. The superior photothermal sensitivity of graphene sheets could be largely explained by their better dispersivity, which has been supported by a simple calculation taking into account thermodynamic, optical and geometrical properties of the two type of carbon nanoparticles. The mechanisms of graphene-mediated photothermal killing of cancer cells apparently involved oxidative stress and mitochondrial membrane depolarization resulting in mixed apoptotic and necrotic cell death characterized by caspase activation/DNA fragmentation and cell membrane damage, respectively. (c) 2010 Elsevier Ltd. All rights reserved.
T2  - Biomaterials
T1  - In vitro comparison of the photothermal anticancer activity of graphene nanoparticles and carbon nanotubes
VL  - 32
IS  - 4
SP  - 1121
EP  - 1129
DO  - 10.1016/j.biomaterials.2010.10.030
ER  - 

@article{
author = "Marković, Zoran M. and Harhaji-Trajković, Ljubica M. and Todorović-Marković, Biljana and Kepić, Dejan P. and Arsikin, Katarina M. and Jovanović, Svetlana P. and Pantovic, Aleksandar C. and Dramićanin, Miroslav and Trajković, Vladimir S.",
year = "2011",
abstract = "The present study compared the photothermal anticancer activity of near-infrared (NIR)-excited graphene nanoparticles and carbon nanotubes (CNT). Despite lower NIR-absorbing capacity, suspension of polyvinylpyrrolidone-coated graphene sheets exposed to NIR radiation (808 nm, 2 W/cm(2)) generated more heat than DNA or sodium dodecylbenzenesulfonate-solubilized single-wall CNT under the same conditions. Accordingly, graphene nanoparticles performed significantly better than CNT in inducing photothermal death of U251 human glioma cells in vitro. The superior photothermal sensitivity of graphene sheets could be largely explained by their better dispersivity, which has been supported by a simple calculation taking into account thermodynamic, optical and geometrical properties of the two type of carbon nanoparticles. The mechanisms of graphene-mediated photothermal killing of cancer cells apparently involved oxidative stress and mitochondrial membrane depolarization resulting in mixed apoptotic and necrotic cell death characterized by caspase activation/DNA fragmentation and cell membrane damage, respectively. (c) 2010 Elsevier Ltd. All rights reserved.",
journal = "Biomaterials",
title = "In vitro comparison of the photothermal anticancer activity of graphene nanoparticles and carbon nanotubes",
volume = "32",
number = "4",
pages = "1121-1129",
doi = "10.1016/j.biomaterials.2010.10.030"
}

Marković, Z. M., Harhaji-Trajković, L. M., Todorović-Marković, B., Kepić, D. P., Arsikin, K. M., Jovanović, S. P., Pantovic, A. C., Dramićanin, M.,& Trajković, V. S.. (2011). In vitro comparison of the photothermal anticancer activity of graphene nanoparticles and carbon nanotubes. in Biomaterials, 32(4), 1121-1129.
https://doi.org/10.1016/j.biomaterials.2010.10.030

Marković ZM, Harhaji-Trajković LM, Todorović-Marković B, Kepić DP, Arsikin KM, Jovanović SP, Pantovic AC, Dramićanin M, Trajković VS. In vitro comparison of the photothermal anticancer activity of graphene nanoparticles and carbon nanotubes. in Biomaterials. 2011;32(4):1121-1129.
doi:10.1016/j.biomaterials.2010.10.030 .

Marković, Zoran M., Harhaji-Trajković, Ljubica M., Todorović-Marković, Biljana, Kepić, Dejan P., Arsikin, Katarina M., Jovanović, Svetlana P., Pantovic, Aleksandar C., Dramićanin, Miroslav, Trajković, Vladimir S., "In vitro comparison of the photothermal anticancer activity of graphene nanoparticles and carbon nanotubes" in Biomaterials, 32, no. 4 (2011):1121-1129,
https://doi.org/10.1016/j.biomaterials.2010.10.030 . .

TY  - JOUR
AU  - Janjetović, Kristina D.
AU  - Vucicevic, Ljubica
AU  - Misirkić, Maja
AU  - Vilimanovich, Urosh
AU  - Tovilovic, Gordana
AU  - Zogovic, Nevena
AU  - Nikolić, Zoran M.
AU  - Jovanović, Svetlana P.
AU  - Bumbaširević, Vladimir Ž.
AU  - Trajković, Vladimir S.
AU  - Harhaji-Trajković, Ljubica M.
PY  - 2011
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/4205
AB  - Metformin is an antidiabetic drug with anticancer properties, which mainly acts through induction of AMP-activated protein kinase (AMPK). In the present study we investigated the influence of metformin on the in vitro anticancer activity of the well-known chemotherapeutic agent cisplatin. Cell viability was determined by MTT and LDH release assay, oxidative stress and apoptosis (caspase activation, DNA fragmentation, and phosphatidylserine exposure) were assessed by flow cytometry, while activation of AMPK and Akt was analyzed by immunoblotting. Although metformin reduced the number of tumour cells when applied alone, it surprisingly antagonized the cytotoxicity of cisplatin towards U251 human glioma, C6 rat glioma, SHSY5Y human neuroblastoma, L929 mouse fibrosarcoma and HL-60 human leukemia cell lines. Only in B16 mouse melanoma cells metformin augmented the cytotoxicity of cisplatin. In U251 glioma cells metformin suppressed cisplatin-induced apoptotic cell death through inhibition of oxidative stress and caspase activation. The observed cytoprotection was apparently AMPK-independent, as metformin did not further increase cisplatin-induced AMPK activation in U251 cells and other pharmacological AMPK activators failed to block cisplatin-mediated apoptosis. On the other hand, metformin induced Akt activation in cisplatin-treated cells and Akt inhibitor 10-DEBC hydrochloride or phosphoinositide 3-kinase/Akt inhibitor LY294002 abolished metformin-mediated antioxidant and antiapoptotic effects. In conclusion, the antidiabetic drug metformin reduces cisplatin in vitro anticancer activity through AMPK-independent upregulation of Akt survival pathway. These data warrant caution when considering metformin for treatment of diabetic cancer patients receiving cisplatin or as a potential adjuvant in cisplatin-based chemotherapeutic regimens. (c) 2010 Published by Elsevier B.V.
T2  - European Journal of Pharmacology
T1  - Metformin reduces cisplatin-mediated apoptotic death of cancer cells through AMPK-independent activation of Akt
VL  - 651
IS  - 1-3
SP  - 41
EP  - 50
DO  - 10.1016/j.ejphar.2010.11.005
ER  - 

@article{
author = "Janjetović, Kristina D. and Vucicevic, Ljubica and Misirkić, Maja and Vilimanovich, Urosh and Tovilovic, Gordana and Zogovic, Nevena and Nikolić, Zoran M. and Jovanović, Svetlana P. and Bumbaširević, Vladimir Ž. and Trajković, Vladimir S. and Harhaji-Trajković, Ljubica M.",
year = "2011",
abstract = "Metformin is an antidiabetic drug with anticancer properties, which mainly acts through induction of AMP-activated protein kinase (AMPK). In the present study we investigated the influence of metformin on the in vitro anticancer activity of the well-known chemotherapeutic agent cisplatin. Cell viability was determined by MTT and LDH release assay, oxidative stress and apoptosis (caspase activation, DNA fragmentation, and phosphatidylserine exposure) were assessed by flow cytometry, while activation of AMPK and Akt was analyzed by immunoblotting. Although metformin reduced the number of tumour cells when applied alone, it surprisingly antagonized the cytotoxicity of cisplatin towards U251 human glioma, C6 rat glioma, SHSY5Y human neuroblastoma, L929 mouse fibrosarcoma and HL-60 human leukemia cell lines. Only in B16 mouse melanoma cells metformin augmented the cytotoxicity of cisplatin. In U251 glioma cells metformin suppressed cisplatin-induced apoptotic cell death through inhibition of oxidative stress and caspase activation. The observed cytoprotection was apparently AMPK-independent, as metformin did not further increase cisplatin-induced AMPK activation in U251 cells and other pharmacological AMPK activators failed to block cisplatin-mediated apoptosis. On the other hand, metformin induced Akt activation in cisplatin-treated cells and Akt inhibitor 10-DEBC hydrochloride or phosphoinositide 3-kinase/Akt inhibitor LY294002 abolished metformin-mediated antioxidant and antiapoptotic effects. In conclusion, the antidiabetic drug metformin reduces cisplatin in vitro anticancer activity through AMPK-independent upregulation of Akt survival pathway. These data warrant caution when considering metformin for treatment of diabetic cancer patients receiving cisplatin or as a potential adjuvant in cisplatin-based chemotherapeutic regimens. (c) 2010 Published by Elsevier B.V.",
journal = "European Journal of Pharmacology",
title = "Metformin reduces cisplatin-mediated apoptotic death of cancer cells through AMPK-independent activation of Akt",
volume = "651",
number = "1-3",
pages = "41-50",
doi = "10.1016/j.ejphar.2010.11.005"
}

Janjetović, K. D., Vucicevic, L., Misirkić, M., Vilimanovich, U., Tovilovic, G., Zogovic, N., Nikolić, Z. M., Jovanović, S. P., Bumbaširević, V. Ž., Trajković, V. S.,& Harhaji-Trajković, L. M.. (2011). Metformin reduces cisplatin-mediated apoptotic death of cancer cells through AMPK-independent activation of Akt. in European Journal of Pharmacology, 651(1-3), 41-50.
https://doi.org/10.1016/j.ejphar.2010.11.005

Janjetović KD, Vucicevic L, Misirkić M, Vilimanovich U, Tovilovic G, Zogovic N, Nikolić ZM, Jovanović SP, Bumbaširević VŽ, Trajković VS, Harhaji-Trajković LM. Metformin reduces cisplatin-mediated apoptotic death of cancer cells through AMPK-independent activation of Akt. in European Journal of Pharmacology. 2011;651(1-3):41-50.
doi:10.1016/j.ejphar.2010.11.005 .

Janjetović, Kristina D., Vucicevic, Ljubica, Misirkić, Maja, Vilimanovich, Urosh, Tovilovic, Gordana, Zogovic, Nevena, Nikolić, Zoran M., Jovanović, Svetlana P., Bumbaširević, Vladimir Ž., Trajković, Vladimir S., Harhaji-Trajković, Ljubica M., "Metformin reduces cisplatin-mediated apoptotic death of cancer cells through AMPK-independent activation of Akt" in European Journal of Pharmacology, 651, no. 1-3 (2011):41-50,
https://doi.org/10.1016/j.ejphar.2010.11.005 . .

TY  - JOUR
AU  - Vucicevic, Ljubica
AU  - Misirkić, Maja
AU  - Janjetović, Kristina D.
AU  - Vilimanovich, Urosh
AU  - Sudar, Emina
AU  - Isenović, Esma R.
AU  - Prica, Marko
AU  - Harhaji-Trajković, Ljubica M.
AU  - Kravić-Stevović, Tamara K.
AU  - Bumbaširević, Vladimir Ž.
AU  - Trajković, Vladimir S.
PY  - 2011
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/4180
AB  - In the present study, we report that compound C, an inhibitor of a key intracellular energy sensor AMP-activated protein kinase (AMPK), can induce autophagy in cancer cells. The induction of autophagy in U251 human glioma cell line was demonstrated by acridine orange staining of intracellular acidic vesicles, Beclin 1 induction, p62 decrease and conversion of LC3-I to autophagosome-associated LC3-II in the presence of proteolysis inhibitors. The presence of autophagosome-like vesicles was confirmed by transmission electron microscopy. Compound C-mediated inhibition of AMPK and raptor in U251 cells was associated with paradoxical decrease in phosphorylation of AMPK/raptor-repressed mTOR, a major negative regulator of autophagy, and its downstream target p70S6K. The phosphorylation of an mTOR activator Akt and the PI3K-activating kinase Src was also impaired in compound C-treated cells. The siRNA-mediated AMPK silencing did not reduce the activity of the Akt/mTOR/p70S6K pathway and AMPK activators metformin and AICAR failed to block compound C-induced autophagy. Autophagy inhibitors bafilomycin and chloroquine significantly increased the cytotoxicity of compound C towards U251 cells, as confirmed by increase in lactate dehydrogenase release, DNA fragmentation and caspase-3 activation. Similar effects of compound C were also observed in C6 rat glioma, L929 mouse fibrosarcoma and B16 mouse melanoma cell lines. Since compound C has previously been reported to suppress AMPK-dependent autophagy in different cell types, our findings suggest that the effects of compound C on autophagy might be dose-, cell type- and/or context-dependent. By demonstrating the ability of compound C to induce autophagic response in cancer cells via AMPK inhibition-independent downregulation of Akt/mTOR pathway, our results warrant caution when using compound C to inhibit AMPK-dependent cellular responses, but also support further exploration of compound C and related molecules as potential anticancer agents.
T2  - Autophagy
T1  - Compound C induces protective autophagy in cancer cells through AMPK inhibition-independent blockade of Akt/mTOR pathway
VL  - 7
IS  - 1
SP  - 40
EP  - 50
DO  - 10.4161/auto.7.1.13883
ER  - 

@article{
author = "Vucicevic, Ljubica and Misirkić, Maja and Janjetović, Kristina D. and Vilimanovich, Urosh and Sudar, Emina and Isenović, Esma R. and Prica, Marko and Harhaji-Trajković, Ljubica M. and Kravić-Stevović, Tamara K. and Bumbaširević, Vladimir Ž. and Trajković, Vladimir S.",
year = "2011",
abstract = "In the present study, we report that compound C, an inhibitor of a key intracellular energy sensor AMP-activated protein kinase (AMPK), can induce autophagy in cancer cells. The induction of autophagy in U251 human glioma cell line was demonstrated by acridine orange staining of intracellular acidic vesicles, Beclin 1 induction, p62 decrease and conversion of LC3-I to autophagosome-associated LC3-II in the presence of proteolysis inhibitors. The presence of autophagosome-like vesicles was confirmed by transmission electron microscopy. Compound C-mediated inhibition of AMPK and raptor in U251 cells was associated with paradoxical decrease in phosphorylation of AMPK/raptor-repressed mTOR, a major negative regulator of autophagy, and its downstream target p70S6K. The phosphorylation of an mTOR activator Akt and the PI3K-activating kinase Src was also impaired in compound C-treated cells. The siRNA-mediated AMPK silencing did not reduce the activity of the Akt/mTOR/p70S6K pathway and AMPK activators metformin and AICAR failed to block compound C-induced autophagy. Autophagy inhibitors bafilomycin and chloroquine significantly increased the cytotoxicity of compound C towards U251 cells, as confirmed by increase in lactate dehydrogenase release, DNA fragmentation and caspase-3 activation. Similar effects of compound C were also observed in C6 rat glioma, L929 mouse fibrosarcoma and B16 mouse melanoma cell lines. Since compound C has previously been reported to suppress AMPK-dependent autophagy in different cell types, our findings suggest that the effects of compound C on autophagy might be dose-, cell type- and/or context-dependent. By demonstrating the ability of compound C to induce autophagic response in cancer cells via AMPK inhibition-independent downregulation of Akt/mTOR pathway, our results warrant caution when using compound C to inhibit AMPK-dependent cellular responses, but also support further exploration of compound C and related molecules as potential anticancer agents.",
journal = "Autophagy",
title = "Compound C induces protective autophagy in cancer cells through AMPK inhibition-independent blockade of Akt/mTOR pathway",
volume = "7",
number = "1",
pages = "40-50",
doi = "10.4161/auto.7.1.13883"
}

Vucicevic, L., Misirkić, M., Janjetović, K. D., Vilimanovich, U., Sudar, E., Isenović, E. R., Prica, M., Harhaji-Trajković, L. M., Kravić-Stevović, T. K., Bumbaširević, V. Ž.,& Trajković, V. S.. (2011). Compound C induces protective autophagy in cancer cells through AMPK inhibition-independent blockade of Akt/mTOR pathway. in Autophagy, 7(1), 40-50.
https://doi.org/10.4161/auto.7.1.13883

Vucicevic L, Misirkić M, Janjetović KD, Vilimanovich U, Sudar E, Isenović ER, Prica M, Harhaji-Trajković LM, Kravić-Stevović TK, Bumbaširević VŽ, Trajković VS. Compound C induces protective autophagy in cancer cells through AMPK inhibition-independent blockade of Akt/mTOR pathway. in Autophagy. 2011;7(1):40-50.
doi:10.4161/auto.7.1.13883 .

Vucicevic, Ljubica, Misirkić, Maja, Janjetović, Kristina D., Vilimanovich, Urosh, Sudar, Emina, Isenović, Esma R., Prica, Marko, Harhaji-Trajković, Ljubica M., Kravić-Stevović, Tamara K., Bumbaširević, Vladimir Ž., Trajković, Vladimir S., "Compound C induces protective autophagy in cancer cells through AMPK inhibition-independent blockade of Akt/mTOR pathway" in Autophagy, 7, no. 1 (2011):40-50,
https://doi.org/10.4161/auto.7.1.13883 . .

TY  - JOUR
AU  - Vucicevic, Ljubica
AU  - Misirkić, Maja
AU  - Janjetović, Kristina D.
AU  - Harhaji-Trajković, Ljubica M.
AU  - Prica, Marko
AU  - Stevanović, Darko
AU  - Isenović, Esma R.
AU  - Sudar, Emina
AU  - Šumarac-Dumanović, Mirjana
AU  - Micic, Dragan
AU  - Trajković, Vladimir S.
PY  - 2009
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/3690
AB  - We investigated the effect of compound C, a well-known inhibitor of the intracellular energy sensor AMP-activated protein kinase (AMPK), on proliferation and viability of human U251 and rat C6 glioma cell lines. Compound C caused G(2)/M cell cycle block, accompanied by apoptotic glioma cell death characterized by caspase activation, phosphatidylserine exposure and DNA fragmentation. The mechanisms underlying the pro-apoptotic action of compound C involved induction of oxidative stress and downregulation of antiapoptotic molecule Bcl-2, while no alteration of pro-apoptotic Bax was observed. Compound C diminished AMPK phosphorylation and enzymatic activity, resulting in reduced phosphorylation of its target acetyl CoA carboxylase. AMPK activators metformin and AICAR partly prevented the cell cycle block, oxidative stress and apoptosis induced by compound C. The small interfering RNA (siRNA) targeting of human AMPK mimicked compound C-induced G(2)/M cell cycle arrest, but failed to induce oxidative stress and apoptosis in U251 glioma cells. In conclusion, our data indicate that AMPK inhibition is required, but not sufficient for compound C-mediated apoptotic death of glioma cells. (c) 2009 Elsevier Inc. All rights reserved.
T2  - Biochemical Pharmacology
T1  - AMP-activated protein kinase-dependent and -independent mechanisms underlying in vitro antiglioma action of compound C
VL  - 77
IS  - 11
SP  - 1684
EP  - 1693
DO  - 10.1016/j.bcp.2009.03.005
ER  - 

@article{
author = "Vucicevic, Ljubica and Misirkić, Maja and Janjetović, Kristina D. and Harhaji-Trajković, Ljubica M. and Prica, Marko and Stevanović, Darko and Isenović, Esma R. and Sudar, Emina and Šumarac-Dumanović, Mirjana and Micic, Dragan and Trajković, Vladimir S.",
year = "2009",
abstract = "We investigated the effect of compound C, a well-known inhibitor of the intracellular energy sensor AMP-activated protein kinase (AMPK), on proliferation and viability of human U251 and rat C6 glioma cell lines. Compound C caused G(2)/M cell cycle block, accompanied by apoptotic glioma cell death characterized by caspase activation, phosphatidylserine exposure and DNA fragmentation. The mechanisms underlying the pro-apoptotic action of compound C involved induction of oxidative stress and downregulation of antiapoptotic molecule Bcl-2, while no alteration of pro-apoptotic Bax was observed. Compound C diminished AMPK phosphorylation and enzymatic activity, resulting in reduced phosphorylation of its target acetyl CoA carboxylase. AMPK activators metformin and AICAR partly prevented the cell cycle block, oxidative stress and apoptosis induced by compound C. The small interfering RNA (siRNA) targeting of human AMPK mimicked compound C-induced G(2)/M cell cycle arrest, but failed to induce oxidative stress and apoptosis in U251 glioma cells. In conclusion, our data indicate that AMPK inhibition is required, but not sufficient for compound C-mediated apoptotic death of glioma cells. (c) 2009 Elsevier Inc. All rights reserved.",
journal = "Biochemical Pharmacology",
title = "AMP-activated protein kinase-dependent and -independent mechanisms underlying in vitro antiglioma action of compound C",
volume = "77",
number = "11",
pages = "1684-1693",
doi = "10.1016/j.bcp.2009.03.005"
}

Vucicevic, L., Misirkić, M., Janjetović, K. D., Harhaji-Trajković, L. M., Prica, M., Stevanović, D., Isenović, E. R., Sudar, E., Šumarac-Dumanović, M., Micic, D.,& Trajković, V. S.. (2009). AMP-activated protein kinase-dependent and -independent mechanisms underlying in vitro antiglioma action of compound C. in Biochemical Pharmacology, 77(11), 1684-1693.
https://doi.org/10.1016/j.bcp.2009.03.005

Vucicevic L, Misirkić M, Janjetović KD, Harhaji-Trajković LM, Prica M, Stevanović D, Isenović ER, Sudar E, Šumarac-Dumanović M, Micic D, Trajković VS. AMP-activated protein kinase-dependent and -independent mechanisms underlying in vitro antiglioma action of compound C. in Biochemical Pharmacology. 2009;77(11):1684-1693.
doi:10.1016/j.bcp.2009.03.005 .

Vucicevic, Ljubica, Misirkić, Maja, Janjetović, Kristina D., Harhaji-Trajković, Ljubica M., Prica, Marko, Stevanović, Darko, Isenović, Esma R., Sudar, Emina, Šumarac-Dumanović, Mirjana, Micic, Dragan, Trajković, Vladimir S., "AMP-activated protein kinase-dependent and -independent mechanisms underlying in vitro antiglioma action of compound C" in Biochemical Pharmacology, 77, no. 11 (2009):1684-1693,
https://doi.org/10.1016/j.bcp.2009.03.005 . .

TY  - JOUR
AU  - Zogovic, Nevena S.
AU  - Nikolić, Nadežda S.
AU  - Vranješ-Đurić, Sanja
AU  - Harhaji, Ljubica M.
AU  - Vucicevic, Ljubica M.
AU  - Janjetović, Kristina D.
AU  - Misirkić, Maja S.
AU  - Todorović-Marković, Biljana
AU  - Marković, Zoran M.
AU  - Milonjić, Slobodan K.
AU  - Trajković, Vladimir S.
PY  - 2009
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/3830
AB  - In the present study, we compared the effects of nanocrystalline fullerene suspension (nanoC(60)) on tumour cell growth in vitro and in vivo. NanoC(60) suspension was prepared by solvent exchange using tetrahydrofuran to dissolve C-60. In vitro, nanoC(60) caused oxidative stress, mitochondrial depolarization and caspase activation, leading to apoptotic and necrotic death in mouse B16 melanoma cells. Bio-distribution studies demonstrated that intraperitoneally injected radiolabeled (I-125) nanoC(60) readily accumulated in the tumour tissue of mice subcutaneously inoculated with B16 cells. However, intraperitoneal administration of nanoC(60) over the course of two weeks starting from melanoma cell implantation not only failed to reduce, but significantly augmented turnout growth. The tumour-promoting effect of nanoC(60) was accompanied by a significant increase in splenocyte production of the immunoregulatory free radical nitric oxide (NO), as well as by a reduction in splenocyte proliferative responses to T- and B-cell mitogens ConcanavalinA and bacterial lipopolysaccharide, respectively. A negative correlation between NO production and splenocyte proliferation indicated a possible role of NO in reducing the proliferation of splenocytes from nanoC(60)-injected mice. These data demonstrate that nanoC(60), in contrast to its potent anticancer activity in vitro, can potentiate tumour growth in vivo, possibly by causing NO-dependent suppression of anticancer immune response. (C) 2009 Elsevier Ltd. All rights reserved.
T2  - Biomaterials
T1  - Opposite effects of nanocrystalline fullerene (C-60) on tumour cell growth in vitro and in vivo and a possible role of immunosupression in the cancer-promoting activity of C-60
VL  - 30
IS  - 36
SP  - 6940
EP  - 6946
DO  - 10.1016/j.biomaterials.2009.09.007
ER  - 

@article{
author = "Zogovic, Nevena S. and Nikolić, Nadežda S. and Vranješ-Đurić, Sanja and Harhaji, Ljubica M. and Vucicevic, Ljubica M. and Janjetović, Kristina D. and Misirkić, Maja S. and Todorović-Marković, Biljana and Marković, Zoran M. and Milonjić, Slobodan K. and Trajković, Vladimir S.",
year = "2009",
abstract = "In the present study, we compared the effects of nanocrystalline fullerene suspension (nanoC(60)) on tumour cell growth in vitro and in vivo. NanoC(60) suspension was prepared by solvent exchange using tetrahydrofuran to dissolve C-60. In vitro, nanoC(60) caused oxidative stress, mitochondrial depolarization and caspase activation, leading to apoptotic and necrotic death in mouse B16 melanoma cells. Bio-distribution studies demonstrated that intraperitoneally injected radiolabeled (I-125) nanoC(60) readily accumulated in the tumour tissue of mice subcutaneously inoculated with B16 cells. However, intraperitoneal administration of nanoC(60) over the course of two weeks starting from melanoma cell implantation not only failed to reduce, but significantly augmented turnout growth. The tumour-promoting effect of nanoC(60) was accompanied by a significant increase in splenocyte production of the immunoregulatory free radical nitric oxide (NO), as well as by a reduction in splenocyte proliferative responses to T- and B-cell mitogens ConcanavalinA and bacterial lipopolysaccharide, respectively. A negative correlation between NO production and splenocyte proliferation indicated a possible role of NO in reducing the proliferation of splenocytes from nanoC(60)-injected mice. These data demonstrate that nanoC(60), in contrast to its potent anticancer activity in vitro, can potentiate tumour growth in vivo, possibly by causing NO-dependent suppression of anticancer immune response. (C) 2009 Elsevier Ltd. All rights reserved.",
journal = "Biomaterials",
title = "Opposite effects of nanocrystalline fullerene (C-60) on tumour cell growth in vitro and in vivo and a possible role of immunosupression in the cancer-promoting activity of C-60",
volume = "30",
number = "36",
pages = "6940-6946",
doi = "10.1016/j.biomaterials.2009.09.007"
}

Zogovic, N. S., Nikolić, N. S., Vranješ-Đurić, S., Harhaji, L. M., Vucicevic, L. M., Janjetović, K. D., Misirkić, M. S., Todorović-Marković, B., Marković, Z. M., Milonjić, S. K.,& Trajković, V. S.. (2009). Opposite effects of nanocrystalline fullerene (C-60) on tumour cell growth in vitro and in vivo and a possible role of immunosupression in the cancer-promoting activity of C-60. in Biomaterials, 30(36), 6940-6946.
https://doi.org/10.1016/j.biomaterials.2009.09.007

Zogovic NS, Nikolić NS, Vranješ-Đurić S, Harhaji LM, Vucicevic LM, Janjetović KD, Misirkić MS, Todorović-Marković B, Marković ZM, Milonjić SK, Trajković VS. Opposite effects of nanocrystalline fullerene (C-60) on tumour cell growth in vitro and in vivo and a possible role of immunosupression in the cancer-promoting activity of C-60. in Biomaterials. 2009;30(36):6940-6946.
doi:10.1016/j.biomaterials.2009.09.007 .

Zogovic, Nevena S., Nikolić, Nadežda S., Vranješ-Đurić, Sanja, Harhaji, Ljubica M., Vucicevic, Ljubica M., Janjetović, Kristina D., Misirkić, Maja S., Todorović-Marković, Biljana, Marković, Zoran M., Milonjić, Slobodan K., Trajković, Vladimir S., "Opposite effects of nanocrystalline fullerene (C-60) on tumour cell growth in vitro and in vivo and a possible role of immunosupression in the cancer-promoting activity of C-60" in Biomaterials, 30, no. 36 (2009):6940-6946,
https://doi.org/10.1016/j.biomaterials.2009.09.007 . .

TY  - JOUR
AU  - Harhaji, Ljubica M.
AU  - Isaković, Aleksandra J.
AU  - Vucicevic, Ljubica
AU  - Janjetović, Kristina D.
AU  - Misirkić, Maja
AU  - Marković, Zoran M.
AU  - Todorović-Marković, Biljana
AU  - Nikolić, Nadežda S.
AU  - Vranješ-Đurić, Sanja
AU  - Nikolić, Zoran M.
AU  - Trajković, Vladimir S.
PY  - 2008
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/3445
AB  - Purpose. The fullerene (C-60/C-70 mixture-C-60/70) nanocrystalline suspension prepared by solvent exchange method using tetrahydrofyran (THF/nC(60/70)) and polyhydroxylated C-60/70 [C-60/70(OH)(n)] were compared for their ability to modulate cytotoxicity of the proinflammatory cytokine tumor necrosis factor (TNT). Materials and Methods. TNF-induced cytotoxicity was assessed in L929 fibrosarcoma cells by crystal violet assay. The type of cell death (apoptosis/necrosis), production of reactive oxygen species, mitochondrial depolarization and caspase activation were determined by flow cytometry using the appropriate reporter dyes. Results. THF/nC(60/70) augmented, while C-60/70(OH)(n) reduced the cytotoxicity of TNF. The numbers of cells undergoing apoptosis/necrosis, as well as of those displaying the activation of apoptosis-inducing enzymes of caspase family, were respectively increased or reduced by THF/nC(60/70) or C-60/70(OH)(n). The antioxidant N-acetylcysteine and mitochondrial permeability transition inhibitor cyclosporin A each partly blocked the cytotoxic action of TNF, indicating the involvement of oxidative stress and mitochondrial dysfunction in the TNF cytotoxicity. Accordingly, THF/nC(60/70) or C-60/70(OH)(n) potentiated or suppressed, respectively, TNF-triggered oxidative stress and mitochondrial depolarization. Conclusion. The ability of different fullerene preparations to modulate TNF-induced oxidative stress and subsequent cell death suggests their potential value in the TNF-based cancer therapy or prevention of TNF-dependent tissue damage.
T2  - Pharmaceutical Research
T1  - Modulation of tumor necrosis factor-mediated cell death by fullerenes
VL  - 25
IS  - 6
SP  - 1365
EP  - 1376
DO  - 10.1007/s11095-007-9486-y
ER  - 

@article{
author = "Harhaji, Ljubica M. and Isaković, Aleksandra J. and Vucicevic, Ljubica and Janjetović, Kristina D. and Misirkić, Maja and Marković, Zoran M. and Todorović-Marković, Biljana and Nikolić, Nadežda S. and Vranješ-Đurić, Sanja and Nikolić, Zoran M. and Trajković, Vladimir S.",
year = "2008",
abstract = "Purpose. The fullerene (C-60/C-70 mixture-C-60/70) nanocrystalline suspension prepared by solvent exchange method using tetrahydrofyran (THF/nC(60/70)) and polyhydroxylated C-60/70 [C-60/70(OH)(n)] were compared for their ability to modulate cytotoxicity of the proinflammatory cytokine tumor necrosis factor (TNT). Materials and Methods. TNF-induced cytotoxicity was assessed in L929 fibrosarcoma cells by crystal violet assay. The type of cell death (apoptosis/necrosis), production of reactive oxygen species, mitochondrial depolarization and caspase activation were determined by flow cytometry using the appropriate reporter dyes. Results. THF/nC(60/70) augmented, while C-60/70(OH)(n) reduced the cytotoxicity of TNF. The numbers of cells undergoing apoptosis/necrosis, as well as of those displaying the activation of apoptosis-inducing enzymes of caspase family, were respectively increased or reduced by THF/nC(60/70) or C-60/70(OH)(n). The antioxidant N-acetylcysteine and mitochondrial permeability transition inhibitor cyclosporin A each partly blocked the cytotoxic action of TNF, indicating the involvement of oxidative stress and mitochondrial dysfunction in the TNF cytotoxicity. Accordingly, THF/nC(60/70) or C-60/70(OH)(n) potentiated or suppressed, respectively, TNF-triggered oxidative stress and mitochondrial depolarization. Conclusion. The ability of different fullerene preparations to modulate TNF-induced oxidative stress and subsequent cell death suggests their potential value in the TNF-based cancer therapy or prevention of TNF-dependent tissue damage.",
journal = "Pharmaceutical Research",
title = "Modulation of tumor necrosis factor-mediated cell death by fullerenes",
volume = "25",
number = "6",
pages = "1365-1376",
doi = "10.1007/s11095-007-9486-y"
}

Harhaji, L. M., Isaković, A. J., Vucicevic, L., Janjetović, K. D., Misirkić, M., Marković, Z. M., Todorović-Marković, B., Nikolić, N. S., Vranješ-Đurić, S., Nikolić, Z. M.,& Trajković, V. S.. (2008). Modulation of tumor necrosis factor-mediated cell death by fullerenes. in Pharmaceutical Research, 25(6), 1365-1376.
https://doi.org/10.1007/s11095-007-9486-y

Harhaji LM, Isaković AJ, Vucicevic L, Janjetović KD, Misirkić M, Marković ZM, Todorović-Marković B, Nikolić NS, Vranješ-Đurić S, Nikolić ZM, Trajković VS. Modulation of tumor necrosis factor-mediated cell death by fullerenes. in Pharmaceutical Research. 2008;25(6):1365-1376.
doi:10.1007/s11095-007-9486-y .

Harhaji, Ljubica M., Isaković, Aleksandra J., Vucicevic, Ljubica, Janjetović, Kristina D., Misirkić, Maja, Marković, Zoran M., Todorović-Marković, Biljana, Nikolić, Nadežda S., Vranješ-Đurić, Sanja, Nikolić, Zoran M., Trajković, Vladimir S., "Modulation of tumor necrosis factor-mediated cell death by fullerenes" in Pharmaceutical Research, 25, no. 6 (2008):1365-1376,
https://doi.org/10.1007/s11095-007-9486-y . .

TY  - JOUR
AU  - Marković, Zoran M.
AU  - Todorović-Marković, Biljana
AU  - Kleut, Duška
AU  - Nikolić, Nadežda S.
AU  - Vranješ-Đurić, Sanja
AU  - Misirkić, Maja
AU  - Vucicevic, Ljubica
AU  - Janjetović, Kristina D.
AU  - Isaković, Aleksandra J.
AU  - Harhaji, Ljubica M.
AU  - Babić-Stojić, Branka S.
AU  - Dramićanin, Miroslav
AU  - Trajković, Vladimir S.
PY  - 2007
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/3322
AB  - Because of the ability to induce cell death in certain conditions, the fullerenes (C-60) are potential anticancer and toxic agents. The colloidal suspension of crystalline C-60 (nano-C-60, nC(60)) is extremely toxic, but the mechanisms of its cytotoxicity are not completely understood. By combining experimental analysis and mathematical modelling, we investigate the requirements for the reactive oxygen species (ROS)-mediated cytotoxicity of different nC(60) suspensions, prepared by solvent exchange method in tetrahydrofuran (THF/nC(60)) and ethanol (EtOH/nC(60)), or by extended mixing in water (aqu/nC(60)). With regard to their capacity to generate ROS and cause mitochondrial depolarization followed by necrotic cell death, the nC(60) suspensions are ranked in the following order: THF/nC(60) GT EtOH/nC(60) GT aqu/nC(60). Mathematical modelling of singlet oxygen (O-1(2)) generation indicates that the O-1(2)-quenching power (THF/nC(60) LT EtOH/nC(60) LT aqU/nC(60)) of the solvent intercalated in the fullerene crystals determines their ability to produce ROS and cause cell damage. These data could. have important implications for toxicology and biomedical application of colloidal fullerenes. (C) 2007 Elsevier Ltd. All rights reserved.
T2  - Biomaterials
T1  - The mechanism of cell-damaging reactive oxygen generation by colloidal fullerenes
VL  - 28
IS  - 36
SP  - 5437
EP  - 5448
DO  - 10.1016/j.biomaterials.2007.09.002
ER  - 

@article{
author = "Marković, Zoran M. and Todorović-Marković, Biljana and Kleut, Duška and Nikolić, Nadežda S. and Vranješ-Đurić, Sanja and Misirkić, Maja and Vucicevic, Ljubica and Janjetović, Kristina D. and Isaković, Aleksandra J. and Harhaji, Ljubica M. and Babić-Stojić, Branka S. and Dramićanin, Miroslav and Trajković, Vladimir S.",
year = "2007",
abstract = "Because of the ability to induce cell death in certain conditions, the fullerenes (C-60) are potential anticancer and toxic agents. The colloidal suspension of crystalline C-60 (nano-C-60, nC(60)) is extremely toxic, but the mechanisms of its cytotoxicity are not completely understood. By combining experimental analysis and mathematical modelling, we investigate the requirements for the reactive oxygen species (ROS)-mediated cytotoxicity of different nC(60) suspensions, prepared by solvent exchange method in tetrahydrofuran (THF/nC(60)) and ethanol (EtOH/nC(60)), or by extended mixing in water (aqu/nC(60)). With regard to their capacity to generate ROS and cause mitochondrial depolarization followed by necrotic cell death, the nC(60) suspensions are ranked in the following order: THF/nC(60) GT EtOH/nC(60) GT aqu/nC(60). Mathematical modelling of singlet oxygen (O-1(2)) generation indicates that the O-1(2)-quenching power (THF/nC(60) LT EtOH/nC(60) LT aqU/nC(60)) of the solvent intercalated in the fullerene crystals determines their ability to produce ROS and cause cell damage. These data could. have important implications for toxicology and biomedical application of colloidal fullerenes. (C) 2007 Elsevier Ltd. All rights reserved.",
journal = "Biomaterials",
title = "The mechanism of cell-damaging reactive oxygen generation by colloidal fullerenes",
volume = "28",
number = "36",
pages = "5437-5448",
doi = "10.1016/j.biomaterials.2007.09.002"
}

Marković, Z. M., Todorović-Marković, B., Kleut, D., Nikolić, N. S., Vranješ-Đurić, S., Misirkić, M., Vucicevic, L., Janjetović, K. D., Isaković, A. J., Harhaji, L. M., Babić-Stojić, B. S., Dramićanin, M.,& Trajković, V. S.. (2007). The mechanism of cell-damaging reactive oxygen generation by colloidal fullerenes. in Biomaterials, 28(36), 5437-5448.
https://doi.org/10.1016/j.biomaterials.2007.09.002

Marković ZM, Todorović-Marković B, Kleut D, Nikolić NS, Vranješ-Đurić S, Misirkić M, Vucicevic L, Janjetović KD, Isaković AJ, Harhaji LM, Babić-Stojić BS, Dramićanin M, Trajković VS. The mechanism of cell-damaging reactive oxygen generation by colloidal fullerenes. in Biomaterials. 2007;28(36):5437-5448.
doi:10.1016/j.biomaterials.2007.09.002 .

Marković, Zoran M., Todorović-Marković, Biljana, Kleut, Duška, Nikolić, Nadežda S., Vranješ-Đurić, Sanja, Misirkić, Maja, Vucicevic, Ljubica, Janjetović, Kristina D., Isaković, Aleksandra J., Harhaji, Ljubica M., Babić-Stojić, Branka S., Dramićanin, Miroslav, Trajković, Vladimir S., "The mechanism of cell-damaging reactive oxygen generation by colloidal fullerenes" in Biomaterials, 28, no. 36 (2007):5437-5448,
https://doi.org/10.1016/j.biomaterials.2007.09.002 . .

TY  - JOUR
AU  - Harhaji, Ljubica M.
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Popadic, Dusan
AU  - Isaković, Aleksandra J.
AU  - Todorović-Marković, Biljana
AU  - Trajković, Vladimir S.
PY  - 2007
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/3225
AB  - We demonstrate the capacity of an herbal anthraquinone aloe emodin to reduce the cytotoxicity of the proinflammatory cytokine tumor necrosis factor (TNF) towards L929 mouse fibrosarcoma and U251 human glioma cell lines. Aloe emodin inhibited both TNF-induced cell necrosis and apoptosis, but it did not reduce cell death induced by UV radiation or hydrogen peroxide. Aloe emodin inhibited both basal and TNF-triggered activation of extracellular signal-regulated kinase (ERK), and a selective blockade of ERK activation mimicked the cytoprotective action of the drug. On the other hand, aloe emodin did not affect TNF-induced activation of p38 mitogen-activated protein kinase or generation of reactive oxygen species. The combination of aloe emodin and TNF caused an intracellular appearance of acidified autophagic vesicles, and the inhibition of autophagy with bafilomycin or 3-methyladenine efficiently blocked the cytoprotective action of aloe emodin. These data indicate that aloe emodin could prevent TNF-triggered cell death through mechanisms involving induction of autophagy and blockade of ERK activation. (C) 2007 Elsevier B.V. All rights reserved.
T2  - European Journal of Pharmacology
T1  - Aloe emodin inhibits the cytotoxic action of tumor necrosis factor
VL  - 568
IS  - 1-3
SP  - 248
EP  - 259
DO  - 10.1016/j.ejphar.2007.04.029
ER  - 

@article{
author = "Harhaji, Ljubica M. and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Popadic, Dusan and Isaković, Aleksandra J. and Todorović-Marković, Biljana and Trajković, Vladimir S.",
year = "2007",
abstract = "We demonstrate the capacity of an herbal anthraquinone aloe emodin to reduce the cytotoxicity of the proinflammatory cytokine tumor necrosis factor (TNF) towards L929 mouse fibrosarcoma and U251 human glioma cell lines. Aloe emodin inhibited both TNF-induced cell necrosis and apoptosis, but it did not reduce cell death induced by UV radiation or hydrogen peroxide. Aloe emodin inhibited both basal and TNF-triggered activation of extracellular signal-regulated kinase (ERK), and a selective blockade of ERK activation mimicked the cytoprotective action of the drug. On the other hand, aloe emodin did not affect TNF-induced activation of p38 mitogen-activated protein kinase or generation of reactive oxygen species. The combination of aloe emodin and TNF caused an intracellular appearance of acidified autophagic vesicles, and the inhibition of autophagy with bafilomycin or 3-methyladenine efficiently blocked the cytoprotective action of aloe emodin. These data indicate that aloe emodin could prevent TNF-triggered cell death through mechanisms involving induction of autophagy and blockade of ERK activation. (C) 2007 Elsevier B.V. All rights reserved.",
journal = "European Journal of Pharmacology",
title = "Aloe emodin inhibits the cytotoxic action of tumor necrosis factor",
volume = "568",
number = "1-3",
pages = "248-259",
doi = "10.1016/j.ejphar.2007.04.029"
}

Harhaji, L. M., Mijatović, S., Maksimović-Ivanić, D., Popadic, D., Isaković, A. J., Todorović-Marković, B.,& Trajković, V. S.. (2007). Aloe emodin inhibits the cytotoxic action of tumor necrosis factor. in European Journal of Pharmacology, 568(1-3), 248-259.
https://doi.org/10.1016/j.ejphar.2007.04.029

Harhaji LM, Mijatović S, Maksimović-Ivanić D, Popadic D, Isaković AJ, Todorović-Marković B, Trajković VS. Aloe emodin inhibits the cytotoxic action of tumor necrosis factor. in European Journal of Pharmacology. 2007;568(1-3):248-259.
doi:10.1016/j.ejphar.2007.04.029 .

Harhaji, Ljubica M., Mijatović, Sanja, Maksimović-Ivanić, Danijela, Popadic, Dusan, Isaković, Aleksandra J., Todorović-Marković, Biljana, Trajković, Vladimir S., "Aloe emodin inhibits the cytotoxic action of tumor necrosis factor" in European Journal of Pharmacology, 568, no. 1-3 (2007):248-259,
https://doi.org/10.1016/j.ejphar.2007.04.029 . .

TY  - JOUR
AU  - Isaković, Aleksandra J.
AU  - Harhaji, Ljubica M.
AU  - Stevanović, D.
AU  - Marković, Zoran M.
AU  - Sumarac-Dumanovic, M.
AU  - Starčević, Vesna
AU  - Micic, D.
AU  - Trajković, Vladimir S.
PY  - 2007
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/3198
AB  - The present study reports for the first time a dual antiglioma effect of the well-known antidiabetic drug metformin. In low-density cultures of the C6 rat glioma cell line, metformin blocked the cell cycle progression in G(0)/G(1) phase without inducing significant cell death. In confluent C6 cultures, on the other hand, metformin caused massive induction of caspase-dependent apoptosis associated with c-Jun N-terminal kinase (JNK) activation, mitochondrial depolarization and oxidative stress. Metformin-triggered apoptosis was completely prevented by agents that block mitochondrial permeability transition (cyclosporin A) and oxygen radical production (N-acetylcisteine), while the inhibitors of JNK activation (SP600125) or glycolysis (sodium fluoride, iodoacetate) provided partial protection. The antiglioma effect of metformin was reduced by compound C, an inhibitor of AMP-activated protein kinase (AMPK), and was mimicked by the AMPK agonist AICAR. Similar effects were observed in the human glioma cell line U251, while rat primary astrocytes were completely resistant to the antiproliferative and proapoptotic action of metformin.
T2  - Cellular and Molecular Life Sciences / CMLS
T1  - Dual antiglioma action of metformin: cell cycle arrest and mitochondria-dependent apoptosis
VL  - 64
IS  - 10
SP  - 1290
EP  - 1302
DO  - 10.1007/s00018-007-7080-4
ER  - 

@article{
author = "Isaković, Aleksandra J. and Harhaji, Ljubica M. and Stevanović, D. and Marković, Zoran M. and Sumarac-Dumanovic, M. and Starčević, Vesna and Micic, D. and Trajković, Vladimir S.",
year = "2007",
abstract = "The present study reports for the first time a dual antiglioma effect of the well-known antidiabetic drug metformin. In low-density cultures of the C6 rat glioma cell line, metformin blocked the cell cycle progression in G(0)/G(1) phase without inducing significant cell death. In confluent C6 cultures, on the other hand, metformin caused massive induction of caspase-dependent apoptosis associated with c-Jun N-terminal kinase (JNK) activation, mitochondrial depolarization and oxidative stress. Metformin-triggered apoptosis was completely prevented by agents that block mitochondrial permeability transition (cyclosporin A) and oxygen radical production (N-acetylcisteine), while the inhibitors of JNK activation (SP600125) or glycolysis (sodium fluoride, iodoacetate) provided partial protection. The antiglioma effect of metformin was reduced by compound C, an inhibitor of AMP-activated protein kinase (AMPK), and was mimicked by the AMPK agonist AICAR. Similar effects were observed in the human glioma cell line U251, while rat primary astrocytes were completely resistant to the antiproliferative and proapoptotic action of metformin.",
journal = "Cellular and Molecular Life Sciences / CMLS",
title = "Dual antiglioma action of metformin: cell cycle arrest and mitochondria-dependent apoptosis",
volume = "64",
number = "10",
pages = "1290-1302",
doi = "10.1007/s00018-007-7080-4"
}

Isaković, A. J., Harhaji, L. M., Stevanović, D., Marković, Z. M., Sumarac-Dumanovic, M., Starčević, V., Micic, D.,& Trajković, V. S.. (2007). Dual antiglioma action of metformin: cell cycle arrest and mitochondria-dependent apoptosis. in Cellular and Molecular Life Sciences / CMLS, 64(10), 1290-1302.
https://doi.org/10.1007/s00018-007-7080-4

Isaković AJ, Harhaji LM, Stevanović D, Marković ZM, Sumarac-Dumanovic M, Starčević V, Micic D, Trajković VS. Dual antiglioma action of metformin: cell cycle arrest and mitochondria-dependent apoptosis. in Cellular and Molecular Life Sciences / CMLS. 2007;64(10):1290-1302.
doi:10.1007/s00018-007-7080-4 .

Isaković, Aleksandra J., Harhaji, Ljubica M., Stevanović, D., Marković, Zoran M., Sumarac-Dumanovic, M., Starčević, Vesna, Micic, D., Trajković, Vladimir S., "Dual antiglioma action of metformin: cell cycle arrest and mitochondria-dependent apoptosis" in Cellular and Molecular Life Sciences / CMLS, 64, no. 10 (2007):1290-1302,
https://doi.org/10.1007/s00018-007-7080-4 . .

TY  - JOUR
AU  - Isaković, Aleksandra J.
AU  - Marković, Zoran M.
AU  - Nikolić, Nadežda S.
AU  - Todorović-Marković, Biljana
AU  - Vranješ-Đurić, Sanja
AU  - Harhaji, Ljubica M.
AU  - Raičević, Nevena
AU  - Romčević, Nebojša Ž.
AU  - Vasiljević-Radović, Dana
AU  - Dramićanin, Miroslav
AU  - Trajković, Vladimir S.
PY  - 2006
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/3076
AB  - We investigated the effect of gamma-irradiation on the cytotoxicity of pure C-60 solubilized in water by using tetrahydrofuran (THF/n-C-60 or THF/n-C-60). In contrast to THF/n-C-60, its gamma-irradiated counterpart failed to generate oxygen radicals and cause extracellular signal-regulated kinase (ERK)-dependent necrotic cell death in various types of mammalian cells. Moreover, gamma-irradiated THF/n-C-60 protected cells from the oxidative stress induced by native THF/n-C-60 or hydrogen peroxide. The observed biological effects were associated with of THF and subsequent derivatization of the n-C-60 surface. These results for the first time demonstrate gamma-irradiation-mediated changes in the physico-chemical properties of THF-prepared nanocrystalline C-60, resulting in a complete loss of its cytotoxic effect and its conversion to a cytoprotective agent. (c) 2006 Elsevier Ltd. All rights reserved.
T2  - Biomaterials
T1  - Inactivation of nanocrystalline C-60 cytotoxicity by gamma-irradiation
VL  - 27
IS  - 29
SP  - 5049
EP  - 5058
DO  - 10.1016/j.biomaterials.2006.05.047
ER  - 

@article{
author = "Isaković, Aleksandra J. and Marković, Zoran M. and Nikolić, Nadežda S. and Todorović-Marković, Biljana and Vranješ-Đurić, Sanja and Harhaji, Ljubica M. and Raičević, Nevena and Romčević, Nebojša Ž. and Vasiljević-Radović, Dana and Dramićanin, Miroslav and Trajković, Vladimir S.",
year = "2006",
abstract = "We investigated the effect of gamma-irradiation on the cytotoxicity of pure C-60 solubilized in water by using tetrahydrofuran (THF/n-C-60 or THF/n-C-60). In contrast to THF/n-C-60, its gamma-irradiated counterpart failed to generate oxygen radicals and cause extracellular signal-regulated kinase (ERK)-dependent necrotic cell death in various types of mammalian cells. Moreover, gamma-irradiated THF/n-C-60 protected cells from the oxidative stress induced by native THF/n-C-60 or hydrogen peroxide. The observed biological effects were associated with of THF and subsequent derivatization of the n-C-60 surface. These results for the first time demonstrate gamma-irradiation-mediated changes in the physico-chemical properties of THF-prepared nanocrystalline C-60, resulting in a complete loss of its cytotoxic effect and its conversion to a cytoprotective agent. (c) 2006 Elsevier Ltd. All rights reserved.",
journal = "Biomaterials",
title = "Inactivation of nanocrystalline C-60 cytotoxicity by gamma-irradiation",
volume = "27",
number = "29",
pages = "5049-5058",
doi = "10.1016/j.biomaterials.2006.05.047"
}

Isaković, A. J., Marković, Z. M., Nikolić, N. S., Todorović-Marković, B., Vranješ-Đurić, S., Harhaji, L. M., Raičević, N., Romčević, N. Ž., Vasiljević-Radović, D., Dramićanin, M.,& Trajković, V. S.. (2006). Inactivation of nanocrystalline C-60 cytotoxicity by gamma-irradiation. in Biomaterials, 27(29), 5049-5058.
https://doi.org/10.1016/j.biomaterials.2006.05.047

Isaković AJ, Marković ZM, Nikolić NS, Todorović-Marković B, Vranješ-Đurić S, Harhaji LM, Raičević N, Romčević NŽ, Vasiljević-Radović D, Dramićanin M, Trajković VS. Inactivation of nanocrystalline C-60 cytotoxicity by gamma-irradiation. in Biomaterials. 2006;27(29):5049-5058.
doi:10.1016/j.biomaterials.2006.05.047 .

Isaković, Aleksandra J., Marković, Zoran M., Nikolić, Nadežda S., Todorović-Marković, Biljana, Vranješ-Đurić, Sanja, Harhaji, Ljubica M., Raičević, Nevena, Romčević, Nebojša Ž., Vasiljević-Radović, Dana, Dramićanin, Miroslav, Trajković, Vladimir S., "Inactivation of nanocrystalline C-60 cytotoxicity by gamma-irradiation" in Biomaterials, 27, no. 29 (2006):5049-5058,
https://doi.org/10.1016/j.biomaterials.2006.05.047 . .

TY  - JOUR
AU  - Isaković, Aleksandra J.
AU  - Marković, Zoran M.
AU  - Todorović-Marković, Biljana
AU  - Nikolić, Nadežda S.
AU  - Vranješ-Đurić, Sanja
AU  - Mirković, Marija D.
AU  - Dramićanin, Miroslav
AU  - Harhaji, Ljubica M.
AU  - Raičević, Nevena
AU  - Nikolić, Zoran M.
AU  - Trajković, Vladimir S.
PY  - 2006
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/3002
AB  - The mechanisms underlying the cytotoxic action of pure fullerene suspension (nano-C-60) and water-soluble polyhydroxylated fullerene [C-60(OH)(n)] were investigated. Crystal violet assay for cell viability demonstrated that nano-C-60 was at least three orders of magnitude more toxic than C-60(OH)(n) to mouse L929 fibrosarcoma, rat C6 glioma, and U251 human glioma cell lines. Flow cytometry analysis of cells stained with propidium iodide (PI), PI/annexin V-fluorescein isothiocyanate, or the redox-sensitive dye dihydrorhodamine revealed that nano-C-60 caused rapid (observable after few hours), reactive oxygen species (ROS)-associated necrosis characterized by cell membrane damage without DNA fragmentation. In contrast, C-60(OH)(n) caused delayed, ROS-independent cell death with characteristics of apoptosis, including DNA fragmentation and loss of cell membrane asymmetry in the absence of increased permeability. Accordingly, the antioxidant N-acetylcysteine protected the cell lines from nano-C-60 toxicity, but not C-60(OH)(n) toxicity, while the pan-caspase inhibitor z-VAD-fmk blocked C-60(OH)(n)-induced apoptosis, but not nano-C-60-mediated necrosis. Finally, C-60(OH)(n) antagonized, while nano-C-60 synergized with, the cytotoxic action of oxidative stress-inducing agents hydrogen peroxide and peroxynitrite donor 3-morpholinosydnonimine. Therefore, unlike polyhydroxylated C-60 that exerts mainly antioxidant/cytoprotective and only mild ROS-independent pro-apoptotic activity, pure crystalline C-60 seems to be endowed with strong pro-oxidant capacity responsible for the rapid necrotic cell death.
T2  - Toxicological Sciences
T1  - Distinct cytotoxic mechanisms of pristine versus hydroxylated fullerene
VL  - 91
IS  - 1
SP  - 173
EP  - 183
DO  - 10.1093/toxsci/kfj127
ER  - 

@article{
author = "Isaković, Aleksandra J. and Marković, Zoran M. and Todorović-Marković, Biljana and Nikolić, Nadežda S. and Vranješ-Đurić, Sanja and Mirković, Marija D. and Dramićanin, Miroslav and Harhaji, Ljubica M. and Raičević, Nevena and Nikolić, Zoran M. and Trajković, Vladimir S.",
year = "2006",
abstract = "The mechanisms underlying the cytotoxic action of pure fullerene suspension (nano-C-60) and water-soluble polyhydroxylated fullerene [C-60(OH)(n)] were investigated. Crystal violet assay for cell viability demonstrated that nano-C-60 was at least three orders of magnitude more toxic than C-60(OH)(n) to mouse L929 fibrosarcoma, rat C6 glioma, and U251 human glioma cell lines. Flow cytometry analysis of cells stained with propidium iodide (PI), PI/annexin V-fluorescein isothiocyanate, or the redox-sensitive dye dihydrorhodamine revealed that nano-C-60 caused rapid (observable after few hours), reactive oxygen species (ROS)-associated necrosis characterized by cell membrane damage without DNA fragmentation. In contrast, C-60(OH)(n) caused delayed, ROS-independent cell death with characteristics of apoptosis, including DNA fragmentation and loss of cell membrane asymmetry in the absence of increased permeability. Accordingly, the antioxidant N-acetylcysteine protected the cell lines from nano-C-60 toxicity, but not C-60(OH)(n) toxicity, while the pan-caspase inhibitor z-VAD-fmk blocked C-60(OH)(n)-induced apoptosis, but not nano-C-60-mediated necrosis. Finally, C-60(OH)(n) antagonized, while nano-C-60 synergized with, the cytotoxic action of oxidative stress-inducing agents hydrogen peroxide and peroxynitrite donor 3-morpholinosydnonimine. Therefore, unlike polyhydroxylated C-60 that exerts mainly antioxidant/cytoprotective and only mild ROS-independent pro-apoptotic activity, pure crystalline C-60 seems to be endowed with strong pro-oxidant capacity responsible for the rapid necrotic cell death.",
journal = "Toxicological Sciences",
title = "Distinct cytotoxic mechanisms of pristine versus hydroxylated fullerene",
volume = "91",
number = "1",
pages = "173-183",
doi = "10.1093/toxsci/kfj127"
}

Isaković, A. J., Marković, Z. M., Todorović-Marković, B., Nikolić, N. S., Vranješ-Đurić, S., Mirković, M. D., Dramićanin, M., Harhaji, L. M., Raičević, N., Nikolić, Z. M.,& Trajković, V. S.. (2006). Distinct cytotoxic mechanisms of pristine versus hydroxylated fullerene. in Toxicological Sciences, 91(1), 173-183.
https://doi.org/10.1093/toxsci/kfj127

Isaković AJ, Marković ZM, Todorović-Marković B, Nikolić NS, Vranješ-Đurić S, Mirković MD, Dramićanin M, Harhaji LM, Raičević N, Nikolić ZM, Trajković VS. Distinct cytotoxic mechanisms of pristine versus hydroxylated fullerene. in Toxicological Sciences. 2006;91(1):173-183.
doi:10.1093/toxsci/kfj127 .

Isaković, Aleksandra J., Marković, Zoran M., Todorović-Marković, Biljana, Nikolić, Nadežda S., Vranješ-Đurić, Sanja, Mirković, Marija D., Dramićanin, Miroslav, Harhaji, Ljubica M., Raičević, Nevena, Nikolić, Zoran M., Trajković, Vladimir S., "Distinct cytotoxic mechanisms of pristine versus hydroxylated fullerene" in Toxicological Sciences, 91, no. 1 (2006):173-183,
https://doi.org/10.1093/toxsci/kfj127 . .