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Enhancement of Cisplatin‐Induced Apoptosis and Caspase 3 Activation by Depletion of Mitochondrial DNA in a Human Osteosarcoma Cell Line
Author(s) -
YEN HSIUCHUAN,
TANG YICHIA,
CHEN FANYI,
CHEN SHIHWEI,
MAJIMA HIDEYUKI J.
Publication year - 2005
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1338.047
Subject(s) - cisplatin , apoptosis , dna fragmentation , cytochrome c , mitochondrial dna , programmed cell death , fragmentation (computing) , mitochondrion , microbiology and biotechnology , cell culture , cancer research , chemistry , cytosol , caspase , caspase 3 , biology , biochemistry , genetics , enzyme , chemotherapy , gene , ecology
A bstract : 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‐ρ 0 ). Results showed that cisplatin decreased cell survival in 143B‐ρ 0 cells. Moreover, cisplatin induced a greater extent of apoptosis‐associated DNA fragmentation and caspase 3 activation in 143B‐ρ 0 cells. The release of mitochondrial cytochrome c into cytosol by cisplatin was enhanced more obviously in 143B cells than in 143B‐ρ 0 cells; however, in the control group of 143B‐ρ 0 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.