Apoptotic effects of ginsenoside Rh2 on human malignant melanoma A375-S2 cells

Acta Pharmacol Sin. 2002 Apr;23(4):315-22.

Abstract

Aim: To study the mechanism of ginsenoside-Rh2 (G-Rh2)-induced growth inhibition of A375-S2 cells.

Methods: A375-S2 cell viability and the effect of caspase inhibitors on G-Rh2-induced apoptosis were measured by crystal violet assay. Changes in cellular morphology were observed by phase-contrast microscopy. Apoptosis-specific nucleosomal DNA fragmentation was assayed by agarose gel electrophoresis. Cell cycle distribution was measured by flow cytometry.

Results: G-Rh2 inhibited the A375-S2 cell growth in concentration- and time-dependent manners. Caspase family inhibitor, z-Val-Ala-Asp-fluoromethylketone (z-VAD-fmk), caspase-3 inhibitor, z-Asp-Glu-Val-Asp-fluoromethylketone (z-DEVD-fmk), and caspase-8 inhibitor, z-Ile-Glu-Asp-fluoromethylketone (z-IETD-fmk), partially inhibited G-Rh2-induced apoptosis. But caspase-1 inhibitor, Ac-Tyr-Val-Ala-Asp-chloromethyl-ketone (Ac-YVAD-cmk), did not antagonize G-Rh2 induced-cell death.

Conclusion: G-Rh2 suppresses the growth of A375-S2 cells in vitro by inducing apoptosis. G-Rh2-induced apoptosis is partially dependent on caspase-8 and caspase-3 pathway in A375-S2 cells. Other apoptotic pathways might be also related to the induction of apoptosis by G-Rh2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Caspase 3
  • Caspase 8
  • Caspase 9
  • Caspase Inhibitors
  • Cell Division / drug effects
  • Cysteine Proteinase Inhibitors / pharmacology
  • Drugs, Chinese Herbal / pharmacology*
  • Ginsenosides / pharmacology*
  • Humans
  • Melanoma / pathology*
  • Oligopeptides / pharmacology
  • Panax / chemistry*
  • Skin Neoplasms / pathology
  • Tumor Cells, Cultured

Substances

  • Caspase Inhibitors
  • Cysteine Proteinase Inhibitors
  • Drugs, Chinese Herbal
  • Ginsenosides
  • Oligopeptides
  • benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone
  • benzyloxycarbonyl-isoleucyl-glutamyl-threonyl-aspartic acid fluoromethyl ketone
  • ginsenoside Rh2
  • CASP3 protein, human
  • CASP8 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 8
  • Caspase 9