Involvement of cytochrome c release and caspase activation in toosendanin-induced PC12 cell apoptosis.
Our previous study showed that toosendanin, a triterpenoid derivative isolated from a Chinese traditional medicine, could induce apoptosis in PC12 cells. In this study we confirmed the apoptosis-inducing effect of toosendanin in PC12 cells with new evidences in morphology and biochemistry: the shrinkage of cytosol, the condensation and fragmentation of nuclei and the formation of DNA ladder. It was also demonstrated that toosendanin decreased the PC12 cell viability in a time- and concentration-dependent manner. To elucidate the pathway linked with the toosendanin-induced apoptosis, the cytochrome c in the cytosol and the cleavage of poly(ADP-ribose) polymerase (PARP) were examined. The obtained results showed that toosendanin caused the release of cytochrome c from mitochondria into the cytosol and then led to the activation of caspase, indicating that the cytochrome c release and caspase activation were involved in the toosendanin-induced apoptosis process. These results suggested the possibility that toosendanin could serve as a candidate for anti-cancer drug.
Tang
Mian-Zhi
MZ
Key Laboratory of Neurobiology, Institute of Physiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
Wang
Zhong-Feng
ZF
Shi
Yu-Liang
YL
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats; D014315:Triterpenes
D020169:Caspases; D045304:Cytochromes c; D004365:Drugs, Chinese Herbal; C036454:toosendanin; D014315:Triterpenes