TY  - CONF
AU  - Murganić, Blagoje
AU  - Kazimir, Aleksandar
AU  - Jelača, Sanja
AU  - Tanić, Nikola
AU  - Hey-Hawkins, Evamarie
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12639
AB  - Background: Estrogen receptor-posiƟ ve (ER+) breast cancer accounts for approximately 70% of all cases and, concordantly, anƟ -estrogen therapies present a leading therapeuƟ c choice. InteresƟ ngly, tamoxifen, which is the most commonly used drug, has also been proven eff ecƟ ve in hormone-independent forms of breast cancer, suggesƟ ng the existence of intracellular off -targets. Frequent acquisiƟ on of therapy resistance presents a plaƞ orm for the design of tamoxifen derivaƟ ves with a 2,2’-bipyridine unit enabling the coordinaƟ on of transiƟ on metal moieƟ es, such as copper(II) dichloride. Copper (Cu) is an essenƟ al element involved in the regulaƟ on of cellular growth and development. DisrupƟ on of its delicate homeostasis results in severe toxicity and hard medical condiƟ ons. Increased demand of cancer cells for this micronutrient makes it a valuable candidate for drug design in cancer treatment. The mechanism of acƟ on of Cu complexes is typically based on their ability to induce deadly oxidaƟ ve stress. This study evaluated the effi cacy of a copper–tamoxifen hybrid drug on a panel of breast cancer cell lines with varying receptor expression status. Material and Methods: The viability of breast adenocarcinoma cell lines MCF-7, MDA-MB-361, MDA-MB-231, 4T1 and glioma U251 was esƟ mated by MTT and CV assays. Flow cytometric analysis of cells stained with annexin V-FITC/propidium iodide, ApoStat, acridine orange, dihydrorhodamine 123 (DHR), dihydroethidium (DHE) or 4-amino-5-methylamino-2’,7’-difl uorofl uorescein diacetate (DAF) was used to evaluate cell death, caspase acƟ vity, autophagy, producƟ on of reacƟ ve oxygen and nitrogen species (ROS/RNS), respecƟ vely. Results: The Cu-tamoxifen hybrid drug displayed substanƟ ally higher hormone-receptor (HR) independent cytotoxic acƟ vity compared to previously reported metal complexes with a similar tamoxifen vector. Massive caspase-dependent apoptoƟ c cell death is parƟ ally aƩ enuated by an autophagic process that counteracts death signals. In contrast to the plaƟ num analogue, the copper-based tamoxifen derivaƟ ve reduces ROS/RNS that may be associated with the intracellular accumulaƟ on of the reduced form of CuI which is important for cuproptosis. Conclusion: This study demonstrates the potenƟ al of the copper–tamoxifen hybrid drug as an intriguing alternaƟ ve to commonly used plaƟ num complexes in treatment of cancer. Its safety and effi ciency will be further esƟ mated in vivo
PB  - Belgrade : Serbian Association for Cancer Research
C3  - Oncology Insights
T1  - Potential of Tamoxifen-based Copper(II) Dichloride in Breast Cancer Therapy
IS  - 1
SP  - 95
EP  - 95
UR  - https://hdl.handle.net/21.15107/rcub_vinar_12639
ER  - 

@conference{
author = "Murganić, Blagoje and Kazimir, Aleksandar and Jelača, Sanja and Tanić, Nikola and Hey-Hawkins, Evamarie and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Background: Estrogen receptor-posiƟ ve (ER+) breast cancer accounts for approximately 70% of all cases and, concordantly, anƟ -estrogen therapies present a leading therapeuƟ c choice. InteresƟ ngly, tamoxifen, which is the most commonly used drug, has also been proven eff ecƟ ve in hormone-independent forms of breast cancer, suggesƟ ng the existence of intracellular off -targets. Frequent acquisiƟ on of therapy resistance presents a plaƞ orm for the design of tamoxifen derivaƟ ves with a 2,2’-bipyridine unit enabling the coordinaƟ on of transiƟ on metal moieƟ es, such as copper(II) dichloride. Copper (Cu) is an essenƟ al element involved in the regulaƟ on of cellular growth and development. DisrupƟ on of its delicate homeostasis results in severe toxicity and hard medical condiƟ ons. Increased demand of cancer cells for this micronutrient makes it a valuable candidate for drug design in cancer treatment. The mechanism of acƟ on of Cu complexes is typically based on their ability to induce deadly oxidaƟ ve stress. This study evaluated the effi cacy of a copper–tamoxifen hybrid drug on a panel of breast cancer cell lines with varying receptor expression status. Material and Methods: The viability of breast adenocarcinoma cell lines MCF-7, MDA-MB-361, MDA-MB-231, 4T1 and glioma U251 was esƟ mated by MTT and CV assays. Flow cytometric analysis of cells stained with annexin V-FITC/propidium iodide, ApoStat, acridine orange, dihydrorhodamine 123 (DHR), dihydroethidium (DHE) or 4-amino-5-methylamino-2’,7’-difl uorofl uorescein diacetate (DAF) was used to evaluate cell death, caspase acƟ vity, autophagy, producƟ on of reacƟ ve oxygen and nitrogen species (ROS/RNS), respecƟ vely. Results: The Cu-tamoxifen hybrid drug displayed substanƟ ally higher hormone-receptor (HR) independent cytotoxic acƟ vity compared to previously reported metal complexes with a similar tamoxifen vector. Massive caspase-dependent apoptoƟ c cell death is parƟ ally aƩ enuated by an autophagic process that counteracts death signals. In contrast to the plaƟ num analogue, the copper-based tamoxifen derivaƟ ve reduces ROS/RNS that may be associated with the intracellular accumulaƟ on of the reduced form of CuI which is important for cuproptosis. Conclusion: This study demonstrates the potenƟ al of the copper–tamoxifen hybrid drug as an intriguing alternaƟ ve to commonly used plaƟ num complexes in treatment of cancer. Its safety and effi ciency will be further esƟ mated in vivo",
publisher = "Belgrade : Serbian Association for Cancer Research",
journal = "Oncology Insights",
title = "Potential of Tamoxifen-based Copper(II) Dichloride in Breast Cancer Therapy",
number = "1",
pages = "95-95",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12639"
}

Murganić, B., Kazimir, A., Jelača, S., Tanić, N., Hey-Hawkins, E., Mijatović, S.,& Maksimović-Ivanić, D.. (2023). Potential of Tamoxifen-based Copper(II) Dichloride in Breast Cancer Therapy. in Oncology Insights
Belgrade : Serbian Association for Cancer Research.(1), 95-95.
https://hdl.handle.net/21.15107/rcub_vinar_12639

Murganić B, Kazimir A, Jelača S, Tanić N, Hey-Hawkins E, Mijatović S, Maksimović-Ivanić D. Potential of Tamoxifen-based Copper(II) Dichloride in Breast Cancer Therapy. in Oncology Insights. 2023;(1):95-95.
https://hdl.handle.net/21.15107/rcub_vinar_12639 .

Murganić, Blagoje, Kazimir, Aleksandar, Jelača, Sanja, Tanić, Nikola, Hey-Hawkins, Evamarie, Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Potential of Tamoxifen-based Copper(II) Dichloride in Breast Cancer Therapy" in Oncology Insights, no. 1 (2023):95-95,
https://hdl.handle.net/21.15107/rcub_vinar_12639 .

TY  - JOUR
AU  - Vodnik, Vesna
AU  - Mojić, Marija
AU  - Stamenović, Una
AU  - Otoničar, Mojca
AU  - Ajdžanović, Vladimir
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Marković, Mirjana
AU  - Barudžija, Tanja
AU  - Filipović, Branko
AU  - Milošević, Verica
AU  - Šošić-Jurjević, Branka
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9749
AB  - Soy isoflavone genistein (Gen) exerts beneficial effects against prostate cancer cells in vitro and in vivo. However, its use as a chemoprevention/therapeutic agent is largely limited due to its low bioavailability. In this study we synthesized two variants of a new delivery system, genistein–gold nanoparticles conjugates Gen@AuNPs1 and Gen@AuNPs2, by an environmentally friendly method, using a dual role of Gen to reduce Au3+ and stabilize the formed AuNPs, with no additional component. The formation of Gen@AuNPs was confirmed via UV–Vis spectroscopy, FTIR, and Raman spectra measurements. The spherical shape and uniform size of Gen@AuNPs1 and Gen@AuNPs2 (10 ± 2 and 23 ± 3 nm, respectively), were determined by transmission electron microscopy. The nano-conjugates also varied in hydrodynamic diameter (65.0 ± 1.7 and 153.0 ± 2.2 nm) but had similar negative zeta potential (−35.0 ± 2.5 and −37.0 ± 1.6 mV), as measured by dynamic light scattering. The Gen loading was estimated to be 46 and 48%, for Gen@AuNPs1 and Gen@AuNPs2, respectively. The antiproliferative activities of GenAuNPs were confirmed by MTT test in vitro on three malignant prostate carcinoma cell lines (PC3, DU 145, and LNCaP), while selectivity toward malignant phenotype was confirmed using non-cancerous MRC-5 cells. Flow cytometric analysis showed that the inhibition on cell proliferation of more potent Gen@AuNPs1 nano-conjugate is comparable with the effects of free Gen. In conclusion, the obtained results, including physicochemical characterization of newly synthesized AuNPs loaded with Gen, cytotoxicity, and IC50 assessments, indicate their stability and bioactivity as an antioxidant and anti-prostate cancer agent, with low toxicity against human primary cells. © 2021 Elsevier B.V.
T2  - Materials Science and Engineering: C
T1  - Development of genistein-loaded gold nanoparticles and their antitumor potential against prostate cancer cell lines
VL  - 124
SP  - 112078
DO  - 10.1016/j.msec.2021.112078
ER  - 

@article{
author = "Vodnik, Vesna and Mojić, Marija and Stamenović, Una and Otoničar, Mojca and Ajdžanović, Vladimir and Maksimović-Ivanić, Danijela and Mijatović, Sanja and Marković, Mirjana and Barudžija, Tanja and Filipović, Branko and Milošević, Verica and Šošić-Jurjević, Branka",
year = "2021",
abstract = "Soy isoflavone genistein (Gen) exerts beneficial effects against prostate cancer cells in vitro and in vivo. However, its use as a chemoprevention/therapeutic agent is largely limited due to its low bioavailability. In this study we synthesized two variants of a new delivery system, genistein–gold nanoparticles conjugates Gen@AuNPs1 and Gen@AuNPs2, by an environmentally friendly method, using a dual role of Gen to reduce Au3+ and stabilize the formed AuNPs, with no additional component. The formation of Gen@AuNPs was confirmed via UV–Vis spectroscopy, FTIR, and Raman spectra measurements. The spherical shape and uniform size of Gen@AuNPs1 and Gen@AuNPs2 (10 ± 2 and 23 ± 3 nm, respectively), were determined by transmission electron microscopy. The nano-conjugates also varied in hydrodynamic diameter (65.0 ± 1.7 and 153.0 ± 2.2 nm) but had similar negative zeta potential (−35.0 ± 2.5 and −37.0 ± 1.6 mV), as measured by dynamic light scattering. The Gen loading was estimated to be 46 and 48%, for Gen@AuNPs1 and Gen@AuNPs2, respectively. The antiproliferative activities of GenAuNPs were confirmed by MTT test in vitro on three malignant prostate carcinoma cell lines (PC3, DU 145, and LNCaP), while selectivity toward malignant phenotype was confirmed using non-cancerous MRC-5 cells. Flow cytometric analysis showed that the inhibition on cell proliferation of more potent Gen@AuNPs1 nano-conjugate is comparable with the effects of free Gen. In conclusion, the obtained results, including physicochemical characterization of newly synthesized AuNPs loaded with Gen, cytotoxicity, and IC50 assessments, indicate their stability and bioactivity as an antioxidant and anti-prostate cancer agent, with low toxicity against human primary cells. © 2021 Elsevier B.V.",
journal = "Materials Science and Engineering: C",
title = "Development of genistein-loaded gold nanoparticles and their antitumor potential against prostate cancer cell lines",
volume = "124",
pages = "112078",
doi = "10.1016/j.msec.2021.112078"
}

Vodnik, V., Mojić, M., Stamenović, U., Otoničar, M., Ajdžanović, V., Maksimović-Ivanić, D., Mijatović, S., Marković, M., Barudžija, T., Filipović, B., Milošević, V.,& Šošić-Jurjević, B.. (2021). Development of genistein-loaded gold nanoparticles and their antitumor potential against prostate cancer cell lines. in Materials Science and Engineering: C, 124, 112078.
https://doi.org/10.1016/j.msec.2021.112078

Vodnik V, Mojić M, Stamenović U, Otoničar M, Ajdžanović V, Maksimović-Ivanić D, Mijatović S, Marković M, Barudžija T, Filipović B, Milošević V, Šošić-Jurjević B. Development of genistein-loaded gold nanoparticles and their antitumor potential against prostate cancer cell lines. in Materials Science and Engineering: C. 2021;124:112078.
doi:10.1016/j.msec.2021.112078 .

Vodnik, Vesna, Mojić, Marija, Stamenović, Una, Otoničar, Mojca, Ajdžanović, Vladimir, Maksimović-Ivanić, Danijela, Mijatović, Sanja, Marković, Mirjana, Barudžija, Tanja, Filipović, Branko, Milošević, Verica, Šošić-Jurjević, Branka, "Development of genistein-loaded gold nanoparticles and their antitumor potential against prostate cancer cell lines" in Materials Science and Engineering: C, 124 (2021):112078,
https://doi.org/10.1016/j.msec.2021.112078 . .

TY  - JOUR
AU  - Čairović, Aleksandra
AU  - Djordjevic, Ivan
AU  - Bulatovic, Mirna
AU  - Mojic, Marija
AU  - Momčilović, Miljana
AU  - Stošić-Grujičić, Stanislava
AU  - Maksimović, Vesna
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Stamenkovic, Dragoslav
PY  - 2013
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/5620
AB  - The aim of this study was to evaluate the effect of recasting of commercially available Ni-Cr (Wiron 99) and Co-Cr (Dentalit C) dental alloys on physiology of microenvironmental cells. The viability of fibrosarcoma (L929) cells, human embrional fibroblasts (MRC-5) and isolated peripheral blood mononuclear cells (PBMC) was measured by MTT and acidic phosphatase tests. Presence of dying cells was estimated by Annexin/PI staining while the production of intracellular nitric oxide (NO), reactive oxygen (ROS) and nitrogen (RNS) species was determined by DAF-FM diacetate and DHR staining. Recasting of Ni-Cr alloy intensified its cytotoxicity manifested through enhanced free radicals production, induction of cell death and permamently diminished cell proliferation. On the other hand, after initial toxic effect cells adapted to the presence of Co-Cr alloys. Independently of recasting, Co-Cr alloys are more compatible with microenvironment then Ni-Cr alloy. Oppositely, recasting of Ni-Cr alloy promoted its toxicity.
T2  - Digest Journal of Nanomaterials and Biostructures
T1  - In Vitro Assessment of Ni-Cr and Co-Cr Dental Alloys Upon Recasting: Cellular Compatibility
VL  - 8
IS  - 2
SP  - 877
EP  - U461
UR  - https://hdl.handle.net/21.15107/rcub_vinar_5620
ER  - 

@article{
author = "Čairović, Aleksandra and Djordjevic, Ivan and Bulatovic, Mirna and Mojic, Marija and Momčilović, Miljana and Stošić-Grujičić, Stanislava and Maksimović, Vesna and Maksimović-Ivanić, Danijela and Mijatović, Sanja and Stamenkovic, Dragoslav",
year = "2013",
abstract = "The aim of this study was to evaluate the effect of recasting of commercially available Ni-Cr (Wiron 99) and Co-Cr (Dentalit C) dental alloys on physiology of microenvironmental cells. The viability of fibrosarcoma (L929) cells, human embrional fibroblasts (MRC-5) and isolated peripheral blood mononuclear cells (PBMC) was measured by MTT and acidic phosphatase tests. Presence of dying cells was estimated by Annexin/PI staining while the production of intracellular nitric oxide (NO), reactive oxygen (ROS) and nitrogen (RNS) species was determined by DAF-FM diacetate and DHR staining. Recasting of Ni-Cr alloy intensified its cytotoxicity manifested through enhanced free radicals production, induction of cell death and permamently diminished cell proliferation. On the other hand, after initial toxic effect cells adapted to the presence of Co-Cr alloys. Independently of recasting, Co-Cr alloys are more compatible with microenvironment then Ni-Cr alloy. Oppositely, recasting of Ni-Cr alloy promoted its toxicity.",
journal = "Digest Journal of Nanomaterials and Biostructures",
title = "In Vitro Assessment of Ni-Cr and Co-Cr Dental Alloys Upon Recasting: Cellular Compatibility",
volume = "8",
number = "2",
pages = "877-U461",
url = "https://hdl.handle.net/21.15107/rcub_vinar_5620"
}

Čairović, A., Djordjevic, I., Bulatovic, M., Mojic, M., Momčilović, M., Stošić-Grujičić, S., Maksimović, V., Maksimović-Ivanić, D., Mijatović, S.,& Stamenkovic, D.. (2013). In Vitro Assessment of Ni-Cr and Co-Cr Dental Alloys Upon Recasting: Cellular Compatibility. in Digest Journal of Nanomaterials and Biostructures, 8(2), 877-U461.
https://hdl.handle.net/21.15107/rcub_vinar_5620

Čairović A, Djordjevic I, Bulatovic M, Mojic M, Momčilović M, Stošić-Grujičić S, Maksimović V, Maksimović-Ivanić D, Mijatović S, Stamenkovic D. In Vitro Assessment of Ni-Cr and Co-Cr Dental Alloys Upon Recasting: Cellular Compatibility. in Digest Journal of Nanomaterials and Biostructures. 2013;8(2):877-U461.
https://hdl.handle.net/21.15107/rcub_vinar_5620 .

Čairović, Aleksandra, Djordjevic, Ivan, Bulatovic, Mirna, Mojic, Marija, Momčilović, Miljana, Stošić-Grujičić, Stanislava, Maksimović, Vesna, Maksimović-Ivanić, Danijela, Mijatović, Sanja, Stamenkovic, Dragoslav, "In Vitro Assessment of Ni-Cr and Co-Cr Dental Alloys Upon Recasting: Cellular Compatibility" in Digest Journal of Nanomaterials and Biostructures, 8, no. 2 (2013):877-U461,
https://hdl.handle.net/21.15107/rcub_vinar_5620 .

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 . .