Cancer Chemopreventive Effects of Cycloartane-Type and Related Triterpenoids in in Vitro and in Vivo Models
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- 作者：Takashi Kikuchi ; Toshihiro Akihisa ; Harukuni Tokuda ; Motohiko Ukiya ; Kenji Watanabe ; Hoyoku Nishino
- 刊名：Journal of Natural Products
- 出版年：2007
- 出版时间：June 2007
- 年：2007
- 卷：70
- 期：6
- 页码：918 - 922
- 全文大小：90K
- 年卷期：v.70,no.6(June 2007)
- ISSN：1520-6025
文摘
Forty-eight natural and semisynthetic cycloartane-type and related triterpenoids have been evaluated for their inhibitoryeffects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells as a primary screening test for anti-tumor promoters. In addition, these triterpenoidshave been tested for their inhibitory effects on activation of (±)-(E)-methtyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexemide (NOR 1), a nitric oxide (NO) donor, as a primary screening test for anti-tumor initiators. All of the compoundstested exhibited inhibitory effects on both EBV-EA and NOR 1 activation. Six of these compounds having a C-24hydroxylated side chain, viz., (24R)-cycloart-25-ene-3
,24-diol (9), (24R)-cycloartane-3,24,25-triol (11), (24S)-cycloartane-3,24,25-triol (12), (24
)-24-methylcycloartane-3,24,241-triol (14), (24)-241-methoxy-24-methylcycloartane-3,24-diol (15), and (24)-24,25-dihydroxycycloartan-3-one (27), showed higher inhibitory effects than the others testedon both EBV-EA (IC50 values of 6.1-7.4 nM) and NOR 1 activation. Furthermore, compounds 14 and 15 exhibitedinhibitory effects on skin tumor promotion in an in vivo two-stage mouse skin carcinogenesis test using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter.
,24-diol (9), (24R)-cycloartane-3,24,25-triol (11), (24S)-cycloartane-3,24,25-triol (12), (24)-24-methylcycloartane-3,24,241-triol (14), (24)-241-methoxy-24-methylcycloartane-3,24-diol (15), and (24)-24,25-dihydroxycycloartan-3-one (27), showed higher inhibitory effects than the others testedon both EBV-EA (IC50 values of 6.1-7.4 nM) and NOR 1 activation. Furthermore, compounds 14 and 15 exhibitedinhibitory effects on skin tumor promotion in an in vivo two-stage mouse skin carcinogenesis test using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter.