Pyrrolizidine alkaloid clivorine induces apoptosis in human normal liver L-02 cells and reduces the expression of p53 protein

Toxicol In Vitro. 2005 Feb;19(1):41-6. doi: 10.1016/j.tiv.2004.06.003.

Abstract

Clivorine, a pyrrolizidine alkaloid, is a potent toxic compound extracted from a Chinese medicinal plant Ligularia hodgsonii Hook. We have previously shown that clivorine inhibited human normal liver L-02 cells proliferation and induced p38 mitogen-activated protein kinase phosphorylation. The aim of this study is to further observe the mechanism of clivorine-inhibited L-02 cells growth. In this paper we show here that clivorine can induce apoptosis in L-02 cells, reduce the expression of p53 protein but has no effect on the expression of Bcl-2 protein, and clivorine also induces the cleavage of the poly(ADP-ribose) polymerase in L-02 cells. Our results suggest that the anti-proliferative function of clivorine in L-02 cells may be due to its inducing cell apoptosis, and clivorine-induced cell apoptosis is independent of p53 protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Asteraceae / chemistry*
  • Bisbenzimidazole
  • Blotting, Western
  • Cell Count
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Flow Cytometry
  • Fluorescent Dyes
  • Hepatocytes / drug effects*
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Humans
  • Plant Extracts / toxicity
  • Poly(ADP-ribose) Polymerases / metabolism
  • Pyrrolizidine Alkaloids / toxicity*
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Fluorescent Dyes
  • Plant Extracts
  • Pyrrolizidine Alkaloids
  • Tumor Suppressor Protein p53
  • Poly(ADP-ribose) Polymerases
  • Bisbenzimidazole
  • clivorine