Etoposide (VP-16) sensitizes p53-deficient human non-small cell lung cancer cells to caspase-7-mediated apoptosis

C. C. Chiu, C. H.M.Y. Lin, K. Fang*


研究成果: 雜誌貢獻期刊論文同行評審

29 引文 斯高帕斯(Scopus)


Human non-small-cell-lung-cancer (NSCLC) cells of p 53-null genotype were exposed to low-dosage topoisomearse II inhibitor etoposide (VP-16). The cellular proliferation rate could be effectively inhibited by VP-16 in dose-dependent manner. The effective drug concentration for growth inhibition could be as low as 0.5 μ M and the apoptotic phenotype became evident 48 h later. In H1299 cells, VP-16-induced cytotoxic effect was demonstrated associated with apoptosis that disappeared when restored with wild-type p53. Cell cycle analysis revealed that, upon VP-16 induction, cell death began with growth arrest by accumulating cells at the G2-M phase. The cells at sub-G1 phase increased at the expense of those at G2-M transition state. To assess the regulation of cell cycle modulators, western blot analysis of H1299 cell lysates showed the release of apoptosis initiator, cytochrome c and apaf-1 hours following drug induction. The cleavage of downstream effectors, procaspase-9 and procaspase-7, but not procaspase-3, was accompanied with proteolysis of poly-(ADP-ribose) polymerase (PARP). VP-16-activated procaspase-7 cleavage was abrogated in cells with ectopically expressed p53.On the other hand, the inhibited procaspase-7 fragmentation by caspase-specific inhibitor reversed apoptotic phenotype caused by drug induction. Thus, VP-16-induced apoptotic cell death was contributed by caspase-7 activation in p 53-deficient human NSCLC cells.

頁(從 - 到)643-650
出版狀態已發佈 - 2005 5月

ASJC Scopus subject areas

  • 藥理
  • 藥學科學
  • 臨床生物化學
  • 細胞生物學
  • 生物化學(醫學)
  • 癌症研究


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