Taipei Medical University

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Ho YS, Tsai PW, Yu CF, Liu HL, Chen RJ and Lin JK
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------>journal_name=Toxicology and Applied Pharmacology.
------>paper_name=Ketoconazole induced apoptosis through p53-dependent pathway in human colorectal and hepatocellular carcinoma cells.
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------>fullAbstract=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 microM) 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.
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------>authors=Ho YS, Tsai PW, Yu CF, Liu HL, Chen RJ and Lin JK
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------>updateTitle=Ketoconazole-induced apoptosis through P53-dependent pathway in human colorectal and hepatocellular carcinoma cell lines.
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------>publish_year=1998
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A B C D E F G H I J K L M N O P Q R S T U V W X Y Z