Anti-tumor-initiating effects of spiro-biflavonoids from Abies sachalinensis.
Cancer chemoprevention, the prevention of cancer by ingestion of chemical agents that reduce the risk of carcinogenesis, is one of the potent ways to reduce morbidity and mortality. We have been searching for cancer chemopreventive agents from the leaves and barks of coniferous trees that have been treated as waste in the forestry industry. We have previously reported the isolation of spiro-biflavonoids, named as abiesinols, and a neolignan from the MeOH extract of the bark of Abies sachalinensis. These compounds were tested for their inhibitory effects on the activation of (±)-(E)-methyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxyhex-3-enamide (NOR 1), a nitric oxide (NO) donor, as a primary screening test for anti-tumor initiators. All compounds tested exhibited potent inhibitory effects on NOR 1 activation. Furthermore, abiesinol A, bearing a spiro-biflavonoid skeleton, showed remarkable anti-tumor-initiating activity in the in vivo two-stage mouse skin carcinogenesis test using peroxynitrite (ONOO(-); PN) as the initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as the promoter.
Wada
Shun-ichi
S
Laboratory of Medicinal Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka, Japan. wada@gly.oups.ac.jp
Hitomi
Teppei
T
Tokuda
Harukuni
H
Tanaka
Reiko
R
D028202:Abies / Q000737:chemistry*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000493:pharmacokinetics*; D044946:Biflavonoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015197:Carcinogenicity Tests; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000187:drug effects; D002478:Cells, Cultured; D003043:Cocarcinogenesis; D005260:Female; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D030421:Peroxynitrous Acid / Q000633:toxicity; D024301:Plant Bark / Q000737:chemistry; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D013141:Spiro Compounds / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity
D016588:Anticarcinogenic Agents; D044946:Biflavonoids; D013141:Spiro Compounds; D030421:Peroxynitrous Acid; D013755:Tetradecanoylphorbol Acetate