Inhibition of tumor-promoting effects by poricoic acids G and H and other lanostane-type triterpenes and cytotoxic activity of poricoic acids A and G from Poria cocos.
The structures of two novel 3,4-seco-lanostane-type triterpenes isolated from the sclerotium of Poria cocos were established to be 16alpha-hydroxy-3,4-seco-lanosta-4(28),8,24-triene-3,21-dioic acid (1; poricoic acid G) and 16alpha-hydroxy-3,4-seco-24-methyllanosta-4(28),8,24(24(1))-triene-3,21-dioic acid (2; poricoic acid H) on the basis of spectroscopic methods. These two, and eight other known compounds isolated from the sclerotium, poricoic acid B (3), poricoic acid A (4), tumulosic acid (5), dehydrotumulosic acid (6), 3-epidehydrotumulosic acid (7), polyporenic acid C (8), 25-hydroxy-3-epidehydrotumulosic acid (9), and dehydroabietic acid methyl ester (10), showed potent inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Evaluation of the cytotoxicity of compounds 1 and 4 against human cancer cell lines revealed that 1 was significantly cytotoxic to leukemia HL-60 cells [GI(50) (concentration that yields 50% growth) value 39.3 nM], although it showed only moderate cytotoxicity to the other cells. Compound 4 exhibited moderate cytotoxicity to all of the cancer cell lines tested.
Ukiya
Motohiko
M
College of Science and Technology, Nihon University, 1-8 Kanda Surugadai, Chiyoda-ku, Tokyo 101-8308, Japan.
Akihisa
Toshihiro
T
Tokuda
Harukuni
H
Hirano
Masaya
M
Oshikubo
Manabu
M
Nobukuni
Yoshitoshi
Y
Kimura
Yumiko
Y
Tai
Takaaki
T
Kondo
Seizo
S
Nishino
Hoyoku
H
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001932:Brain Neoplasms; D002851:Chromatography, High Pressure Liquid; D003110:Colonic Neoplasms; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007564:Japan; D007680:Kidney Neoplasms; D007810:Lanosterol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D007951:Leukemia, Myeloid; D008175:Lung Neoplasms; D008545:Melanoma; D008968:Molecular Conformation; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010051:Ovarian Neoplasms; D010946:Plants, Medicinal / Q000737:chemistry*; D011124:Polyporaceae / Q000737:chemistry*; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D014315:Triterpenes; C455165:poricoic acid A; C455167:poricoic acid G; C455166:poricoic acid H; D007810:Lanosterol