Cancer preventive potential of trichothecenes from Trichothecium roseum.
Bioassay-guided separation of extracts from the culture broth and mycelium of the fungus Trichothecium roseum, aiming at the discovery for cancer preventive agents, resulted in the isolation of three new trichothecene sesquiterpenes, trichothecinols A-C (1-3) together with three known analogues, trichothecin (4), trichodermol (5) and trichothecolone (6). Compounds 1-6 exhibited remarkably potent inhibition against Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). Further compound 1 strongly inhibited TPA-induced tumor promotion on mouse skin initiated with 7,12-dimethylbenz[a]anthracene (DMBA) in two-stage carcinogenesis tests. These results suggest that compound 1 might be a valuable lead for further evaluation as a cancer preventive agent. In addition to their cancer preventive activity, compound 2 was found to show modest antifungal activity against Crypotcoccus albidus and Saccharomyces cerevisiae.
Konishi
Kazuhide
K
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Iida
Akira
A
Kaneko
Masafumi
M
Tomioka
Kiyoshi
K
Tokuda
Harukuni
H
Nishino
Hoyoku
H
Kumeda
Yuko
Y
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology; D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000956:Antigens, Viral / Q000187:drug effects; D015197:Carcinogenicity Tests; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D051379:Mice; D003904:Mitosporic Fungi / Q000737:chemistry*; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010212:Papilloma / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D012878:Skin Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity; D014255:Trichothecenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000890:Anti-Infective Agents; D016588:Anticarcinogenic Agents; D000956:Antigens, Viral; C033305:Epstein-Barr virus early antigen; D014255:Trichothecenes; D013755:Tetradecanoylphorbol Acetate