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Korean Journal of Obstetrics & Gynecology 2003;46(10):1989-1998.
Published online October 1, 2003.
The Study of the Cytotoxic Mechanism of Cisplatin in HeLa Cells.
Joung Ho Choi, Hun Cho, Sun Young Lee, Seong Hwan Oh, Heung Gon Kim, Rae Gil Park
1Department of Obstetrics and Gynecology, College of Medicine, Wonkwang University, Iksan, Korea.
2Department of Microbiology, College of Medicine, Wonkwang University, Iksan, Korea.
Abstract
Cis-diamminedichloroplatinum II (cisplatin) has been reported to induce cell death. However, the mechanism by which cisplatin is induced the apoptosis of cancer cells is still unclear. To evaluate the mechanistic insights of apoptosis by cisplatin, we tested the activities of apoptotic signaling pathway in HeLa cells. Apoptotic death of HeLa cells by cisplatin was confirmed by ladder-pattern fragmentation of genomic DNA. Cisplatin induced the activation of caspase-3 and 9 proteases in a time dependent manner. The caspase-3 protease activation and the cleavage of poly (ADP-ribose) polymerase (PARP) and procaspase-3 was demonstrated. We also showed that the expression of Bcl-2 and Bcl-xL was markedly decreased by the addition of cisplatin in HeLa cells. Moreover, expression of Fas and FasL proteins was increased by cisplatin. These data suggest that cisplatin triggers the activation of apoptotic signaling pathway in human cervical cancer, HeLa cells, via affects the expression of Fas, FasL and Bcl-2 families as well as triggers the activation of caspase-3 and -9 proteases.
Key Words: Cisplatin, HeLa cells, Apoptosis, Caspase-3 and 9 proteases


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