AMP-activated protein kinase-dependent and -independent mechanisms underlying in vitro antiglioma action of compound C
Samo za registrovane korisnike
2009
Autori
Vucicevic, LjubicaMisirkić, 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.
Članak u časopisu
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
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.
Ključne reči:
Glioma / AMPK / Compound C / Apoptosis / Oxidative stressIzvor:
Biochemical Pharmacology, 2009, 77, 11, 1684-1693Finansiranje / projekti:
- Ministry of Science of the Republic of Serbia [145073, 145067, 143030]
DOI: 10.1016/j.bcp.2009.03.005
ISSN: 0006-2952
PubMed: 19428322
WoS: 000265768300004
Scopus: 2-s2.0-64449084511
Kolekcije
Institucija/grupa
VinčaTY - 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 . .