title: Cucurbitane triterpenoids from the leaves of Momordica charantia, and their cancer chemopreventive effects and cytotoxicities.
abstract: Seventeen cucurbitane-type triterpenoids, 1-17, including six new compounds, (23E)-3β,25-dihydroxy-7β-methoxycucurbita-5,23-dien-19-al (1), (23S*)-3β-hydroxy-7β,23-dimethoxycucurbita-5,24-dien-19-al (6), (23R*)-23-O-methylmomordicine IV (7), (25ξ)-26-hydroxymomordicoside L (8), 25-oxo-27-normomordicoside L (9), and 25-O-methylkaravilagenin D (12), were isolated from a MeOH extract of the leaves of Japanese Momordica charantia. The structures of new compounds were elucidated on the basis of extensive spectroscopic analyses and comparison with literature. Compounds 1-17 were examined for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced with 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, a known primary screening test for inhibitors of tumor promotion. Four compounds, 1, (23E)-3β,7β-dihydroxy-25-methoxycucurbita-5,23-dien-19-al (2), karavilagenin D (11), and 12, showed potent inhibitory effects on EBV-EA induction with IC(50) values in the range of 242-264 mol ratio/32 pmol TPA. In addition, compounds 1 and 11 exhibited inhibitory effects on skin-tumor promotion in an in vivo two-stage mouse skin carcinogenesis test based on 7,12-dimethylbenz[a]anthracene (DMBA) as initiator, and with TPA as a promoter. Furthermore, upon evaluation of the cytotoxic activities of compounds 1-17 against human cancer cell lines, compounds 2, 5-7, 9, and 14 showed potent activities against HL60 cell line, and compound 2 against SK-BR-3 cell line.
authors.affiliation: College of Science and Technology, Nihon University, 1-8-14 Kanda Surugadai, Chiyoda-ku, Tokyo, Japan.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Takashi
authors.initials: T
authors.lastname: Kikuchi
authors.forename: Harukuni
authors.initials: H
authors.lastname: Tokuda
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Suzuki
authors.forename: Kei-ichiro
authors.initials: K
authors.lastname: Inafuku
authors.forename: Motofumi
authors.initials: M
authors.lastname: Miura
authors.forename: Shigeyasu
authors.initials: S
authors.lastname: Motohashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Akihisa
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D000956:Antigens, Viral / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D006027:Glycosides / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D029777:Momordica charantia / Q000737:chemistry*; D018515:Plant Leaves / Q000737:chemistry*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000956:Antigens, Viral; D000972:Antineoplastic Agents, Phytogenic; D002273:Carcinogens; C033305:Epstein-Barr virus early antigen; D006027:Glycosides; D014315:Triterpenes; C514277:cucurbitane; D015127:9,10-Dimethyl-1,2-benzanthracene; D013755:Tetradecanoylphorbol Acetate