Enhancement of cisplatin-induced apoptosis and caspase 3 activation by depletion of mitochondrial DNA in a human osteosarcoma cell line

Hsiu Chuan Yen*, Yi Chia Tang, Fan Yi Chen, Shih Wei Chen, Hideyuki J. Majima

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

27 Scopus citations

Abstract

Cisplatin is an anticancer drug that can induce apoptosis. In this study, we investigated the effect of mitochondrial DNA (mtDNA) depletion on cisplatin-induced cell death using a human osteosarcoma cell line (143B) and mtDNA-depleted 143B cells (143B-p°). Results showed that cisplatin decreased cell survival in 143B-p° cells. Moreover, cisplatin induced a greater extent of apoptosis-associated DNA fragmentation and caspase 3 activation in 143B-p° cells. The release of mitochondrial cytochrome c into cytosol by cisplatin was enhanced more obviously in 143B cells than in 143B-p° cells; however, in the control group of 143B-p cells, it was already dramatically greater. Depletion of mtDNA may increase sensitivity of cells to cisplatin-induced apoptosis by enhancing caspase 3 activation via both cytochrome c-dependent and -independent pathways.

Original languageEnglish
Pages (from-to)516-522
Number of pages7
JournalAnnals of the New York Academy of Sciences
Volume1042
DOIs
StatePublished - 2005

Keywords

  • Apoptosis
  • Caspase 3
  • Cisplatin
  • Cytochrome c
  • Mitochondrial DNA

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