Anti-tumor-promoting effects of 25-methoxyporicoic acid A and other triterpene acids from Poria cocos.
Nine new (1, 3, 5, 8, 12, 13, 15, 17, and 18) and nine known (2, 4, 6, 7, 9-11, 14, and 16) lanostane-type triterpene acids and a known diterpene acid (19) were isolated from the epidermis of the sclerotia of Poria cocos. The structures of the new compounds were established as 16alpha,27-dihydroxydehyrotrametenoic acid (1), 25-hydroxy-3-epitumulosic acid (3), 16alpha,25-dihydroxyeburiconic acid (5), 25-methoxyporicoic acid A (8), 26-hydroxyporicoic acid DM (12), 25-hydroxyporicoic acid C (13), poricoic acid GM (15), poricoic acid HM (17), and 6,7-dehydroporicoic acid H (18), on the basis of spectroscopic methods. On evaluation of the nine new and two of the known compounds, 4 and 19, against the Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, all of the compounds exhibited inhibitory effects, with IC(50) values in the range 187-348 mol ratio/32 pmol TPA. In addition, compound 8 exhibited an inhibitory effect on skin tumor promotion in an in vivo two-stage carcinogenesis test using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter. Further, 17 compounds, 1-14, 16, 18, and 19, were evaluated for their cytotoxic activity against two human tumor cell lines, HL60 (leukemia) and CRL1579 (melanoma).
Akihisa
Toshihiro
T
College of Science and Technology, Nihon University, 1-8 Kanda Surugadai, Chiyoda-ku, Tokyo 101-8308, Japan. akihisa@chem.cst.nihon-u.ac.jp
Uchiyama
Emiko
E
Kikuchi
Takashi
T
Tokuda
Harukuni
H
Suzuki
Takashi
T
Kimura
Yumiko
Y
D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000956:Antigens, Viral / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D007810:Lanosterol / Q000031:analogs & derivatives / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D015394:Molecular Structure; D055441:Poria / Q000737:chemistry*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
C545041:25-methoxyporicoic acid A; D016588:Anticarcinogenic Agents; D000956:Antigens, Viral; C033305:Epstein-Barr virus early antigen; D014315:Triterpenes; D007810:Lanosterol; D013755:Tetradecanoylphorbol Acetate