Enhancement of cisplatin-induced apoptosis and caspase 3 activation by depletion of mitochondrial DNA in a human osteosarcoma cell line.
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.
Yen
Hsiu-Chuan
HC
Graduate Institute of Medical Biotechnology, Chang Gung University, 259 Wen-Hwa 1st Rd., Kwei-Shan, Tao-Yuan 333, Taiwan. yen@mail.cgu.edu.tw
Tang
Yi-Chia
YC
Chen
Fan-Yi
FY
Chen
Shih-Wei
SW
Majima
Hideyuki J
HJ
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*
D004272:DNA, Mitochondrial; D009707:Nucleosomes; D045304:Cytochromes c; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D002945:Cisplatin