INHIBITION OF TUMOR PROMOTION IN SENCAR MOUSE SKIN BY ETHANOL EXTRACTOF ZINGIBER-OFFICINALE RHIZOME

There is considerable emphasis on identifying potential chemopreventiv e agents present in food consumed by the human population. Ginger rhiz ome (Zingiber officinale), known commonly as ginger, is consumed world wide in cookeries as a spice and a flavoring agent. In prior in vitro studies, it has been shown that the water or organic solvent extract o f ginger possesses antioxidative and antiinflammatory properties. In t his study, we evaluated whether ethanol extract of ginger (GE) possess es anti-tumor-promoting effects in a mouse skin tumorigenesis model. B ecause skin tumor promoters induced epidermal ornithine decarboxylase (ODC), cyclooxygenase, and lipoxygenase activities, and edema and hype rplasia are conventionally used markers of skin tumor promotion, first , we assessed the effect of GE on these parameters. Preapplication of GE onto the skin of SENCAR mice resulted in significant inhibition of 12-O-tetradecanoylphorbol-13-acetate (TPA)-caused induction of epiderm al ODC, cyclooxygenase, and lipoxygenase activities and ODC mRNA expre ssion in a dose-dependent manner. Preapplication of GE to mouse skin a lso afforded significant inhibition of TPA-caused epidermal edema (56% ) and hyperplasia (44%). In long-term tumor studies, topical applicati on of GE 30 min prior to that of each TPA application to 7,12-dimethyl benz(a)anthracene-initiated SENCAR mice resulted in a highly significa nt protection against skin tumor incidence and its subsequent multipli city. The animals pretreated with GE showed substantially lower tumor body burdens compared with non-GE-treated controls. The results of our study, for the first time, provide clear evidence that GE possesses a nti-skin tumor-promoting effects, and that the mechanism of such effec ts may involve inhibition of tumor promoter-caused cellular, biochemic al, and molecular changes in mouse skin.