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.
Footnotes
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Abbreviations: DEVE-CHO, N-acetyl-Asp-Glu-Val-Asp-al; DMSO, dimethyl sulfoxide; FBS, fetal bovine serum; IC50, 50% growth-inhibitory concentration; I. obliquus, Inonotus obliquus (Pers.: Fr.) Pilat [Fuscoporia obliqua (Pers.: Fr.) Aoshima]; inotodiol, lanosta-8,24-diene-3β,22R-diol; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; % ILS, percentage increase in life-span; tramentenolic acid, 3β-hydroxylanosta-8,24-dien-21-oic acid.
- Received April 21, 2008.
- Revision received June 12, 2008.
- Accepted June 25, 2008.
- Copyright© 2008 International Institute of Anticaner Research (Dr. John G. Delinassios), All rights reserved