Inotodiol, a Lanostane Triterpenoid, from Inonotus obliquus Inhibits Cell Proliferation through Caspase-3-dependent Apoptosis

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 μM). A caspase-3 inhibitor, DEVD-CHO (N-acetyl-Asp-Glu-Val-Asp-al, 100 μM) 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.