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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Citations (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.

Original languageEnglish
Pages (from-to)643-650
Number of pages8
Issue number3
Publication statusPublished - 2005 May


  • Cell cycle and apoptosis
  • Etoposide
  • Human non-small-cell-lung-cancer cells
  • VP-16

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Cancer Research


Dive into the research topics of 'Etoposide (VP-16) sensitizes p53-deficient human non-small cell lung cancer cells to caspase-7-mediated apoptosis'. Together they form a unique fingerprint.

Cite this