| Co-Investigator(Kenkyū-buntansha) |
TOKUDA Harukuni Kyoto Prefectural University of Medicine, Department of Biochemistry, Assistant Professor, 生化学教室, 助手 (60111960)
YASUKAWA Ken Nihon University, College of Pharmacy, Professor, 薬学部, 教授 (00130625)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
Six azaphilones, monascin (1), ankaflavin (2), rubropunctatin (3), monascorburin (4), rubropunctamine (5), and monascorburamine (6), two furanoisophthalides, xanthomonasin A (7) and xanthomonasin B (8), and two amino acids, (+)-monascumic acid (9) and (-)-monascumic acid (10), isolated from the extracts of Monascus pilosus-fermented rice (red-mold rice) were evaluated for their inhibitory effects on 12-O-tetradecanoylphorbol-13-acetate(TPA)-induced inflammation in mice, on the induction of Epstein-Barr virus early antigen(EBV-EA) by TPA in Raji cells, and on the activation of (±)-(E)-methyl-2[(E)-hydroxy-imino]-5-nitro-6-methoxy-3-hexemide (NOR 1), a nitric oxide(NO) donor. Among the compounds tested, seven compounds (1-6,and 10) on TPA-induced inflammation, and six compounds (1,3-5,9,and 10) on EBV-EA activation, exhibited potent inhibitory effects. All of the compounds tested showed moderate inhibitory effects on NOR 1 activation. Compound 1 was further evaluated for its anti-tumor-initiating activity via oral administration on the two-stage carcinogenesis of mouse skin tumor induced by peroxynitrite (ONOO^-;PN) or by ultraviolet light B(UVB) as an initiator and 12-O-tetradecanoylphorbol-13-acetate(TPA) as a promoter. Compound 1 exhibited marked inhibitory activity on both PN and UVB induced mouse skin carcinogenesis tests. These findings suggest that compound 1 may be valuable as potential cancer chemopreventive agents in chemical and environmental carcinogenesis.
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