Inhibitory effects of new types of biflavonoid-related polyphenols; lophirone A and lophiraic acid, on some tumor promoter-induced biological responses in vitro and in vivo.
Lophirone A, isolated as a new type of biflavonoid-related inhibitor of Epstein-Barr virus (EBV) activation, was tested for further inhibitory properties against tumor promotion by short-term system. Lophirone A (200 micrograms) significantly inhibited inflammation of mouse ear (inhibitory effect (IE) = 70%) by 12-O-hexadecanoyl-16-hydroxyphorbol-13-acetate (HHPA, 2 micrograms). It also inhibited both Ca(2+)- and phospholipid-dependent protein kinase C (PKC) activation by 12-O-tetradecanoylphorbol-13-acetate (TPA, IC50 = 50 microM). Application of lophirone A (160 nmol) reduced the number of tumors per mouse (IE = 85%) in an initiation-promotion experiment using dimethylbenz[a]anthracene (DMBA, 0.19 mumol) and TPA (1.6 nmol) on ICR mouse skin. Lophiraic acid, a related polyphenol, was negative in all of the short-term tests. An important chemical factor which may reduce the activities of flavonoid class of inhibitors for tumor promotion was indicated.
Murakami
A
A
Department of Food Science and Technology, Faculty of Agriculture, Kyoto University, Japan.
Ohigashi
H
H
Jisaka
M
M
Hirota
M
M
Irie
R
R
Koshimizu
K
K
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D003043:Cocarcinogenesis; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010212:Papilloma / Q000139:chemically induced / Q000517:prevention & control*; D010636:Phenols / Q000494:pharmacology*; D011108:Polymers / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051381:Rats; D011921:Rats, Inbred WKY; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D013755:Tetradecanoylphorbol Acetate
D001578:Benzopyrans; D005419:Flavonoids; D010636:Phenols; D011108:Polymers; C069396:lophirone A; C069397:lophiraic acid; D015127:9,10-Dimethyl-1,2-benzanthracene; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate