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

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)39-47
Number of pages9
JournalToxicology and Applied Pharmacology
Volume153
Issue number1
DOIs
Publication statusPublished - 1998 Nov

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Pharmacology

Fingerprint Dive into the research topics of 'Ketoconazole-induced apoptosis through P53-dependent pathway in human colorectal and hepatocellular carcinoma cell lines'. Together they form a unique fingerprint.

  • Cite this