NAKANO Kimiko University of Tokushima, Faculty of Pharmaceutical Sciences, Research Assistant, 薬学部, 助手 (20136279)
SHISHIDO Kozo University of Tokushima, Faculty of Pharmaceutical Sciences, Proffesor, 薬学部, 教授 (20006349)
|Budget Amount *help
¥7,200,000 (Direct Cost : ¥7,200,000)
Fiscal Year 1995 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1994 : ¥1,200,000 (Direct Cost : ¥1,200,000)
Fiscal Year 1993 : ¥5,300,000 (Direct Cost : ¥5,300,000)
Recently, studies on antitumor promoting activities have been reported detailing the inhibitory effects of several natural products on 12-O-tetradecanoylphorbol-13-acetate(TPA)induced Epstein-Barr virus early antigen(EBV-EA)activation. Tripterygium wilfordii Hook fil.has been used as an anticancer drug in China for hundreds of years. We have been studying the sesquiterpene constituents of some Celastraceae plants.We isolated about 50 new compounds from T.wilfordii Hook fil.var.regelii and Euonymus sieboldianus.
To search for possible antitumor pormoters, we examined the inhibitory tendency of these compounds on EBV-EA activation. Some of these sesquiterpenes were observed to significantly inhibit the EBV-EA activation allow doses. Next, we attempted to test the cytotoxicity of these compounds, because it is important to develop a reagent for chemoprevention against cancer. Several compounds did not show any cytotoxicity. Above findings indicate that these compounds might be valuable antitumor promoters.
Next, we tried to test in vivo two-stage carcinogenic test of mouse skin. Triptogelin A-1, one of the active compounds, exhibited remarkable inhibitory effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. Furthermore, triptogelin A-1 showed inhibitory effects in two stage carcinogenesis test in mouse lung.
We evaluated sesquiterpenes for their antiviral activities, one of them, triptofordin C-2, was found to be active against herpes simplex virus type I and human cytomegalovirus. We suggest possible mechanisms of action of the compound.We also isolated new compounds from Celastraceae plants.These findings ndicated that data focus attention on possible exploitation of information for cancer preventive agent development.