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01-10-2011 | PRECLINICAL STUDIES

Apoptotic induction by simvastatin in human lung cancer A549 cells via Akt signaling dependent down-regulation of survivin

Authors: Ki-Eun Hwang, Kyoung-Suk Na, Do-Sim Park, Keum-Ha Choi, Byoung-Ryun Kim, Hyeok Shim, Eun-Taik Jeong, Hak-Ryul Kim

Published in: Investigational New Drugs | Issue 5/2011

Summary

Statins, HMG-CoA reductase inhibitors have been studied for their antiproliferative and proapototic effects. Recently, statin-induced apoptosis has been associated with down-regulation of survivin expression in cancer cells. However, the mechanism of deregulated survivin by simvastatin on lung cancer is still unclear. Herein, we demonstrated that simvastatin induced caspase-dependent apoptosis in A549 lung cancer cells. Simvastatin also resulted in a decrease in the expression of phosphorylated Akt. In addition, simvastatin effectively down-regulated survivin mRNA and protein, but not cIAP-1 and cIAP-2. The combination of simvastatin and 10 μM LY294002 (non-toxic dose) augmented apoptosis significantly, as evidenced by cleavage of PARP. The immunoreactive band of survivin was markedly decreased in cells treated with 50 μM LY294002 (toxic dose) as well as by the combination of simvastatin and 10 μM LY294002. Moreover, survivin down-regulation by RNA interference induced apoptosis accompanied by an increase in hypodiploid DNA content. Taken together, these data suggest that the anti-cancer effect of simvastatin via induction of apoptosis is related to Akt signaling dependent down-regulation of survivin in lung cancer A549 cells.

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Title: Apoptotic induction by simvastatin in human lung cancer A549 cells via Akt signaling dependent down-regulation of survivin
Authors: Ki-Eun Hwang
Kyoung-Suk Na
Do-Sim Park
Keum-Ha Choi
Byoung-Ryun Kim
Hyeok Shim
Eun-Taik Jeong
Hak-Ryul Kim
Publication date: 01-10-2011
Publisher: Springer US
Published in: Investigational New Drugs / Issue 5/2011
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-010-9450-2

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