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 . .