Inotodiol, a lanostane triterpenoid, from Inonotus obliquus inhibits cell proliferation through caspase-3-dependent apoptosis

Anticancer Res. Sep-Oct 2008;28(5A):2691-6.

Abstract

Background: To investigate the antitumor effect of Inonotus obliquus Pilat, the antiproliferative effect of lanostane triterpenoids from a chloroform extract of I. obliquus sclerotia against mouse leukemia P388 cells was assessed.

Materials and methods: Cell viability was measured by MTT assay. Caspase-3/7 activity and DNA fragmentation were evaluated to analyze apoptosis induction. The in vivo antitumor effect was evaluated by the number of survival days of mouse leukemia P388-bearing female CDF1 mice.

Results: The chloroform extract of I. obliquus sclerotia inhibited proliferation of the P388 cells. Among the triterpenoids examined, only inotodiol inhibited P388 cell proliferation. DNA fragmentation and caspase-3/7 activation were observed in the P388 cells treated with inotodiol (30 microM). A caspase-3 inhibitor, DEVD-CHO (N-acetyl-Asp-Glu-Val-Asp-al, 100 microM) partially inhibited the DNA fragmentation and growth-inhibition induced by inotodiol. The intraperitoneal administration of 10 mg/kg inotodiol prolonged the number of survival days of the P388-bearing mice.

Conclusion: Inotodiol inhibits cell proliferation through apoptosis induction by activating caspase-3.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Basidiomycota / chemistry
  • Caspase 3 / metabolism*
  • Cell Growth Processes / drug effects
  • Enzyme Activation / drug effects
  • Female
  • Lanosterol / analogs & derivatives*
  • Lanosterol / pharmacology
  • Leukemia P388 / drug therapy*
  • Leukemia P388 / enzymology
  • Leukemia P388 / pathology
  • Mice

Substances

  • inotodiol
  • Lanosterol
  • Caspase 3