Autophagy contributes to apoptosis in A20 and EL4 lymphoma cells treated with fluvastatin

Cancer Cell International

Soo-Ki Kim³  Dong-Qing Cai²  Soon-Bong Song¹  Cheol-Su Kim⁴  Kyu-Jae Lee¹  Dong-Heui Kim¹  Xu-Feng Qi² 

[1] Department of Environmental Medical Biology, Yonsei University Wonju College of Medicine, Wonju, Gangwon, 220-701, South Korea;Department of Developmental & Regenerative Biology, Ji Nan University School of Life Science and Technology, Guangzhou, 510632, People’s Republic of China;Institute of Basic Medical Science, Yonsei University Wonju College of Medicine, Wonju, Gangwon 220-701, South Korea;Department of Microbiology, Yonsei University Wonju College of Medicine, Wonju, Gangwon 220-701, South Korea

关键词: Mevalonate pathway;    Autophagy;    Apoptosis;    Lymphoma cells;    Fluvastatin;   

Others  :  792656
DOI  :  10.1186/1475-2867-13-111

 received in 2013-04-07, accepted in 2013-10-31,  发布年份 2013

【 摘 要 】

Convincing evidence indicates that statins stimulate apoptotic cell death in several types of proliferating tumor cells in a cholesterol-lowering-independent manner. However, the relationship between apoptosis and autophagy in lymphoma cells exposed to statins remains unclear. The objective of this study was to elucidate the potential involvement of autophagy in fluvastatin-induced cell death of lymphoma cells. We found that fluvastatin treatment enhanced the activation of pro-apoptotic members such as caspase-3 and Bax, but suppressed the activation of anti-apoptotic molecule Bcl-2 in lymphoma cells including A20 and EL4 cells. The process was accompanied by increases in numbers of annexin V alone or annexin V/PI double positive cells. Furthermore, both autophagosomes and increases in levels of LC3-II were also observed in fluvastatin-treated lymphoma cells. However, apoptosis in fluvastatin-treated lymphoma cells could be blocked by the addition of 3-methyladenine (3-MA), the specific inhibitor of autophagy. Fluvastatin-induced activation of caspase-3, DNA fragmentation, and activation of LC3-II were blocked by metabolic products of the HMG-CoA reductase reaction, such as mevalonate, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). These results suggest that autophagy contributes to fluvastatin-induced apoptosis in lymphoma cells, and that these regulating processes require inhibition of metabolic products of the HMG-CoA reductase reaction including mevalonate, FPP and GGPP.

【 授权许可】

   
2013 Qi et al.; licensee BioMed Central Ltd.

【 图 表 】

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