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

研究成果: Article同行評審

38 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English
頁(從 - 到)39-47
頁數9
期刊Toxicology and Applied Pharmacology
153
發行號1
DOIs
出版狀態Published - 1998 11月

All Science Journal Classification (ASJC) codes

  • 毒理學
  • 藥理

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