Inhibition of tumor promotion in SENCAR mouse skin by ethanol extract of Zingiber officinale rhizome.
There is considerable emphasis on identifying potential chemopreventive agents present in food consumed by the human population. Ginger rhizome (Zingiber officinale), known commonly as ginger, is consumed worldwide 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 of ginger possesses antioxidative and antiinflammatory properties. In this study, we evaluated whether ethanol extract of ginger (GE) possesses anti-tumor-promoting effects in a mouse skin tumorigenesis model. Because skin tumor promoters induced epidermal ornithine decarboxylase (ODC), cyclooxygenase, and lipoxygenase activities, and edema and hyperplasia 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 12-0-tetradecanoylphorbol-13-acetate (TPA)-caused induction of epidermal ODC, cyclooxygenase, and lipoxygenase activities and ODC mRNA expression in a does-dependent manner. Preapplication of GE to mouse skin also afforded significant inhibition of TPA-caused epidermal edema (56%) and hyperplasia (44%). In long-term tumor studies, topical application of GE 30 min prior to that of each TPA application to 7,12-dimethylbenz(a)anthracene-initiated SENCAR mice resulted in a highly significant protection against skin tumor incidence and its subsequent multiplicity. 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 anti-skin tumor-promoting effects, and that the mechanism of such effects may involve inhibition of tumor promoter-caused cellular, biochemical, and molecular changes in mouse skin.
Katiyar
S K
SK
Department of Dermatology, Skin Diseases Research Center, University Hospitals of Cleveland, Case Western Reserve University, Ohio 44106, USA.
Agarwal
R
R
Mukhtar
H
H
D000279:Administration, Cutaneous; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D008084:Lipoxygenase / Q000096:biosynthesis*; D051379:Mice; D018632:Mice, Inbred SENCAR; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D010936:Plant Extracts / Q000008:administration & dosage; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D012867:Skin / Q000201:enzymology* / Q000473:pathology; D012878:Skin Neoplasms / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D017365:Spices
D000970:Antineoplastic Agents; D010936:Plant Extracts; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D009955:Ornithine Decarboxylase