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


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.


CONCLUSIONS
Inotodiol inhibits cell proliferation through apoptosis induction by activating caspase-3.
Nomura
Masaaki
M
Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Ishikawa 920-1181, Japan.
Takahashi
Tatsuo
T
Uesugi
Aimi
A
Tanaka
Reiko
R
Kobayashi
Shinjiro
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001487:Basidiomycota / Q000737:chemistry; D053148:Caspase 3 / Q000378:metabolism*; D048708:Cell Growth Processes / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D007810:Lanosterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D007941:Leukemia P388 / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D051379:Mice
C517091:inotodiol; D007810:Lanosterol; D053148:Caspase 3