Ketoconazole-induced apoptosis through P53-dependent pathway in human colorectal and hepatocellular carcinoma cell lines

Yuan Soon Ho, Pei Wen Tsai, Cheng Fei Yu, Hsu Ling Liu, Rong Jane Chen, Jen Kun Lin

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35 引文 斯高帕斯(Scopus)

摘要

In this study, we first demonstrated that the widely used oral antifungal drug, ketoconazole (KT), can induce apoptosis in various type of human cancer cells and in a primary culture of rat liver cells. We further investigated the molecular mechanisms of KT-induced apoptosis. It was found that KT induced nuclear accumulation of p53 protein in a dose- and time- dependent manner. The level of p53 protein was elevated approximately three times as much in treated cells 24 h after KT (5 μM) exposure as in cells receiving mock treatment. We found that cells containing wild-type p53 (COLO 205 and Hep G2) were more sensitive to KT exposure. The bax protein was induced and the bcl-2 protein was inhibited by KT in cells containing wild- type p53 (Hep G2, COLO 205) but not in cells without p53 (Hep 3B). The caspase-3 was activated 24 h after KT treatment. The Poly-(ADP ribose)polymerase (PARP) and the lamin A degradation was induced by KT, which promoted nuclear membrane disassembly and eventually caused apoptosis. Our results also indicated that none of the PKC gene family was involved in KT- induced apoptosis.

原文英語
頁(從 - 到)39-47
頁數9
期刊Toxicology and Applied Pharmacology
153
發行號1
DOIs
出版狀態已發佈 - 1998

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

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