1'-Acetoxychavicol acetate, a superoxide anion generation inhibitor, potently inhibits tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in ICR mouse skin.
The anti-tumor-promoting activity of 1'-acetoxychavicol acetate (ACA) was examined in a two-stage carcinogenesis experiment in ICR mouse skin using 7,12-dimethylbenz[a]anthracene (0.19 mumol) and 12-O-tetradecanoylphorbol-13-acetate (TPA; 1.6 nmol). Topical application of ACA (160 nmol) markedly reduced the average number of tumors per mouse and the ratio of tumor-bearing mice: inhibition ratios 90% (p < 0.001) and 42% (p < 0.005), respectively. ACA even at a dose equimolar to TPA (1.6 nmol) significantly reduced the average number of tumors per mouse: inhibitory ratio 44% (p < 0.05). ACA potently inhibited TPA-induced superoxide (O2-) generation in differentiated HL-60 cells (IC50 = 4.3 microM) and suppressed the lipid hydroperoxide formation by 42% (p < 0.001) in the ethyl linoleate autoxidation test.
Murakami
A
A
Department of Biotechnological Science, Faculty of Biology-Oriented Science and Technology, Kinki University, Wakayama, Japan.
Ohura
S
S
Nakamura
Y
Y
Koshimizu
K
K
Ohigashi
H
H
D000818:Animals; D000838:Anions; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D001592:Benzyl Alcohols; D002273:Carcinogens; D005260:Female; D018922:HL-60 Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008041:Linoleic Acids; D008054:Lipid Peroxides / Q000032:analysis / Q000378:metabolism; D008315:Malondialdehyde / Q000032:analysis / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013729:Terpenes / Q000627:therapeutic use*; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors*; D019820:Xanthine; D014969:Xanthine Oxidase / Q000378:metabolism; D014970:Xanthines / Q000378:metabolism
D000838:Anions; D016588:Anticarcinogenic Agents; D000975:Antioxidants; D001592:Benzyl Alcohols; D002273:Carcinogens; D008041:Linoleic Acids; D008054:Lipid Peroxides; D013729:Terpenes; D014970:Xanthines; D013481:Superoxides; D019820:Xanthine; D008315:Malondialdehyde; D014969:Xanthine Oxidase; C007678:ethyl linoleate; D013755:Tetradecanoylphorbol Acetate; C047948:1'-acetoxychavicol acetate