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

Xu Feng Qi, Dong Heui Kim, Kyu Jae Lee, Cheol Su Kim, Soon Bong Song, Dong Qing Cai, Soo Ki Kim

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number111
JournalCancer Cell International
Volume13
Issue number1
DOIs
Publication statusPublished - 2013 Nov 8

All Science Journal Classification (ASJC) codes

  • Genetics
  • Oncology
  • Cancer Research

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