Release of cytochrome c from isolated mitochondria by etoposide.
The efficacy of chemotherapeutic agents on tumor cells has been shown to be modulated by tumor suppressor gene p53 and its target genes such as Bcl-2 family members (Bax, Noxa, and PUMA). However, various chemotherapeutic agents can induce cell death in tumor cells that do not express the functional p53, suggesting that some chemotherapeutic agents may induce cell death in a p53-independent pathway. Here we showed that etoposide can induce the similar degree of cell death in p53-deficient HCT 116 cells, whereas 5'-FU-mediated cell death is strongly dependent on the existence of functional p53 in HCT 116 cells. Further, we provide the evidence that etoposide can induce the cytochrome c release from isolated mitochondria, and etoposide-induced cytochrome c release is not accompanied with the large amplitude swelling of mitochondria. These data suggest that etoposide can directly induce the mitochondrial dysfunction irrespective of p53 status, and it may, at least in part, account for the p53-independent pathway in cell death induced by chemotherapeutic agents.
Park
Jung-Hee
JH
Department of Biochemistry, Chosun University School of Medicine, Dong-Gu, Gwangju, Korea.
Kim
Tae-Hyoung
TH
D000818:Animals; D016923:Cell Death / Q000502:physiology; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism*; D005047:Etoposide / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D016159:Tumor Suppressor Protein p53; D005047:Etoposide; D045304:Cytochromes c