title: Cancer chemopreventive activity of 3beta-methoxyserrat-14-en-21beta-ol and several serratane analogs on two-stage mouse skin carcinogenesis.
abstract: 3beta-Methoxyserrat-14-en-21beta-ol (1) and 3alpha-methoxyserrat-14-en-21beta-ol (2) are the most abundant triterpenoids from two Picea plants, Picea jezoensis (Sieb. et Zucc.) Carr. var. jezoensis and P. jezoensis (Sieb. et Zucc.) Carr. hondoensis (Mayr) Rehder, and the total yield of 1 and 2 reach over 1/3 of the chloroform extract of the above two plants. This study deals with the potential of anti-tumor promoting activity of 1 and results of the assay of 22 synthetic serratane-type triterpenoids (6)-(27) derived from 1, 2, 21-episerratenediol (3), diepiserratenediol (4) and 13alpha,14alpha-epoxy-3beta-methoxyserratan-21beta-ol (5) to discuss the structure-activity relationship. As a preliminary evaluation of their potential to inhibit tumor promotion, the inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) were used. All compounds except for 12 and 19 showed potent inhibitory effects on EBV-EA induction (100% inhibition at 1000 mol ratio/TPA), their effects being stronger than that of a positive control oleanolic acid. Compounds 1, 13, 14, 18, 20 and 26 were selected to examine the effect on the in vivo two-stage mouse skin carcinogenesis test induced by 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter. The most abundant triterpenoid 1 and the synthetic compounds 13 and 14 were found to exhibit the excellent anti-tumor promoting activity in the in vivo carcinogenesis test, and compounds 18, 20 and 26 also showed strong inhibitory effects.
authors.affiliation: Department of Medicinal Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan. tanakar@gly.oups.ac.jp
authors.forename: Reiko
authors.initials: R
authors.lastname: Tanaka
authors.forename: Kandasamy
authors.initials: K
authors.lastname: Shanmugasundaram
authors.forename: Chiharu
authors.initials: C
authors.lastname: Yamaguchi
authors.forename: Yohei
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: Harukuni
authors.initials: H
authors.lastname: Tokuda
authors.forename: Kiyoharu
authors.initials: K
authors.lastname: Nishide
authors.forename: Manabu
authors.initials: M
authors.lastname: Node
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D004195:Disease Models, Animal; D004354:Drug Screening Assays, Antitumor; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D010212:Papilloma / Q000517:prevention & control* / Q000662:veterinary; D028222:Picea / Q000737:chemistry; D012878:Skin Neoplasms / Q000517:prevention & control* / Q000662:veterinary; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: C492953:3beta-methoxyserrat-14-en-21beta-ol; D014315:Triterpenes