Antitumor-promoting effects and cytotoxic activities of dammar resin triterpenoids and their derivatives.
Nineteen known triterpenoids, 1-19, and one known sesquiterpenoid, 20, were isolated from dammar resin obtained from Shorea javanica K. & V. (Dipterocarpaceae). One of the acidic triterpenoids, dammarenolic acid (1), was converted to fourteen derivatives, namely, an alcohol, 21, an aldehyde, 22, and twelve L-amino acid conjugates, 23-34. Compounds 1-34 were examined for their inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by 12-O-tetradecanoylphorbol 13-acetate (TPA) in Raji cells, a known primary screening test for antitumor promoters. All of the compounds tested, except for compounds 4, 5, 12-14, 16, and 17, showed inhibitory effects against EBV-EA activation with potencies either comparable with or stronger than that of beta-carotene, a known natural antitumor promoter. In addition, (20S)-20-hydroxy-3,4-secodammara-4(28),24-dien-3-al (22) 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 promoter. Furthermore, evaluation of the cytotoxic activities of compounds 1-34 against human cancer cell lines showed that reduction (i.e., 21 and 22) or conjugation with L-amino acids (i.e., 23-34) of compound 1 enhanced the cytotoxicity against human melanoma cell line CRL1579.
Ukiya
Motohiko
M
College of Science and Technology, Nihon University, 1-8 Kanda Surugadai, Chiyoda-ku, Tokyo 101-8308, Japan. ukiya@chem.cst.nihon-u.ac.jp
Kikuchi
Takashi
T
Tokuda
Harukuni
H
Tabata
Keiichi
K
Kimura
Yumiko
Y
Arai
Takanari
T
Ezaki
Yoichiro
Y
Oseto
Osamu
O
Suzuki
Takashi
T
Akihisa
Toshihiro
T
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053958:Dipterocarpaceae / Q000737:chemistry; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D010212:Papilloma / Q000188:drug therapy; D012116:Resins, Plant / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity*; D012878:Skin Neoplasms / Q000188:drug therapy; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity*
D000970:Antineoplastic Agents; D012116:Resins, Plant; D014315:Triterpenes