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

Ann N Y Acad Sci. 2005 May;1042:516-22. doi: 10.1196/annals.1338.047.

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-rho0). Results showed that cisplatin decreased cell survival in 143B-rho0 cells. Moreover, cisplatin induced a greater extent of apoptosis-associated DNA fragmentation and caspase 3 activation in 143B-rho0 cells. The release of mitochondrial cytochrome c into cytosol by cisplatin was enhanced more obviously in 143B cells than in 143B-rho0 cells; however, in the control group of 143B-rho0 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Caspase 3
  • Caspases / metabolism*
  • Cell Line, Tumor
  • Cisplatin / pharmacology*
  • Cytochromes c / metabolism
  • DNA, Mitochondrial / genetics
  • Enzyme Activation / drug effects
  • Gene Deletion*
  • Humans
  • Mitochondria / drug effects
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Nucleosomes / drug effects
  • Nucleosomes / genetics
  • Osteosarcoma / enzymology*
  • Osteosarcoma / genetics
  • Osteosarcoma / pathology*

Substances

  • DNA, Mitochondrial
  • Nucleosomes
  • Cytochromes c
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • Cisplatin