title: Enhancement of cisplatin-induced apoptosis and caspase 3 activation by depletion of mitochondrial DNA in a human osteosarcoma cell line.
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.
authors.affiliation: Graduate Institute of Medical Biotechnology, Chang Gung University, 259 Wen-Hwa 1st Rd., Kwei-Shan, Tao-Yuan 333, Taiwan. yen@mail.cgu.edu.tw
authors.forename: Hsiu-Chuan
authors.initials: HC
authors.lastname: Yen
authors.forename: Yi-Chia
authors.initials: YC
authors.lastname: Tang
authors.forename: Fan-Yi
authors.initials: FY
authors.lastname: Chen
authors.forename: Shih-Wei
authors.initials: SW
authors.lastname: Chen
authors.forename: Hideyuki J
authors.initials: HJ
authors.lastname: Majima
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects; D017353:Gene Deletion; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D009707:Nucleosomes / Q000187:drug effects / Q000235:genetics; D012516:Osteosarcoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*
chemical_list: D004272:DNA, Mitochondrial; D009707:Nucleosomes; D045304:Cytochromes c; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D002945:Cisplatin