Inhibition of 12-O-tetradecanoylphorbol-13-acetate-caused tumor promotion in benzo[a]pyrene-initiated CD-1 mouse skin by geniposide.
The effects of topical application of geniposide on 12-o-tetradecanoylphorbol-13-acetate(TPA)-induced promotion of skin tumors, hyperplasia, ornithine decarboxylase (ODC) and inflammation were evaluated in female CD-1 mice. Topical application of geniposide (0.2 to 1.0 mumol) with TPA (15 nmol) twice weekly for 20 weeks to mice previously initiated with benzo[a]pyrene (B[a]P) inhibited the number of TPA-induced tumor per mouse by 84 or 89%, respectively. Pre-application of the same amount of geniposide also afforded significant protection against TPA-induced hyperplasia in the ear skin. Topical application of geniposide inhibited tumor promoter-caused induction of epidermal ODC activity by TPA (5 nmol). The topical application of geniposide (0.2 or 1.0 mumol) inhibited TPA-induced edema of mouse ears by 41 or 43%, respectively. Pretreatment of mouse skin with various amounts of geniposide caused inhibition of hydrogen peroxide (H2O2) and myeloperoxidase (MPO) formation by TPA. These results indicate that geniposide possesses potential as a cancer chemopreventive agent against tumor promotion.
Lee
M J
MJ
Institute of Biochemistry, Chung Shan Medical and Dental College, Taichung, Taiwan, R.O.C.
Hsu
J D
JD
Wang
C J
CJ
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001564:Benzo(a)pyrene / Q000633:toxicity; D003043:Cocarcinogenesis; D004428:Ear Neoplasms / Q000139:chemically induced / Q000517:prevention & control; D005260:Female; D006861:Hydrogen Peroxide / Q000378:metabolism; D006965:Hyperplasia; D039823:Iridoids; D051379:Mice; D009955:Ornithine Decarboxylase / Q000032:analysis; D009195:Peroxidase / Q000378:metabolism; D011714:Pyrans / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors* / Q000633:toxicity
D016588:Anticarcinogenic Agents; D039823:Iridoids; D011714:Pyrans; C007835:geniposide; D001564:Benzo(a)pyrene; D006861:Hydrogen Peroxide; D009195:Peroxidase; D009955:Ornithine Decarboxylase; D013755:Tetradecanoylphorbol Acetate