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

Fingerprint

Ketoconazole
Hepatocellular Carcinoma
Colorectal Neoplasms
Cells
Apoptosis
Cell Line
Lamin Type A
bcl-2-Associated X Protein
Proteins
Poly(ADP-ribose) Polymerases
Nuclear Envelope
Cell culture
Caspase 3
Liver
Rats
Genes
Membranes
Degradation

Keywords

  • Apoptosis
  • Bax
  • Ketoconazole
  • Lamin A.
  • PARP

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Ketoconazole-induced apoptosis through P53-dependent pathway in human colorectal and hepatocellular carcinoma cell lines. / Ho, Yuan Soon; Tsai, Pei Wen; Yu, Cheng Fei; Liu, Hsu Ling; Chen, Rong Jane; Lin, Jen Kun.

In: Toxicology and Applied Pharmacology, Vol. 153, No. 1, 1998, p. 39-47.

Research output: Contribution to journalArticle

Ho, Yuan Soon ; Tsai, Pei Wen ; Yu, Cheng Fei ; Liu, Hsu Ling ; Chen, Rong Jane ; Lin, Jen Kun. / Ketoconazole-induced apoptosis through P53-dependent pathway in human colorectal and hepatocellular carcinoma cell lines. In: Toxicology and Applied Pharmacology. 1998 ; Vol. 153, No. 1. pp. 39-47.
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