Our laboratory has been studying
cancer chemopreventive effects of polyphenolic fraction isolated from
green tea (
GTP). In prior studies we have shown that (a)
GTP possesses antigenotoxic effects in various test systems; (b) topical application of
GTP protects against UV radiation and chemical
carcinogen-induced
tumorigenesis in murine skin; and (c) feeding of
GTP in
drinking water p.o. to mice protects against
carcinogen-induced forestomach and lung
tumorigenesis. Recently, we showed that in a dose-dependent manner
GTP inhibits
tumor promoter-caused induction of epidermal
ornithine decarboxylase activity in SENCAR mice (R. Agarwal et al.,
Cancer Res., 52: 3582-3588, 1992). In the present study, we assessed the effect of
GTP on TPA-induced skin
tumor promotion in 7,12-dimethylbenz(a)anthracene-initiated SENCAR mouse. Topical application of varying doses of
GTP (1-24 mg) 30 min prior to that of each TPA application resulted in highly significant protection against skin
tumor promotion in a dose-dependent manner. The animals pretreated with
GTP showed substantially lower
tumor body burden such as decrease in total number of
tumors per group, number of
tumors per animal,
tumor volume per mouse, and average volume per
tumor, as compared to the animals that did not receive
GTP. Since TPA-induced epidermal
cyclooxygenase and
lipoxygenase activities and
edema and
hyperplasia are conventionally used markers of skin
tumor promotion, we also assessed the effect of preapplication of
GTP on these parameters. As quantitated by the formation of
prostaglandin and hydroxy-eicosatetraenoic
acid metabolites from, respectively,
cyclooxygenase- and
lipoxygenase-catalyzed metabolism of
arachidonic acid, skin application of
GTP to SENCAR mice resulted in significant inhibition of TPA-caused effects on these 2
enzymes. Prior application of
GTP to mouse skin also resulted in 30-46% inhibition of TPA-induced epidermal
edema and
hyperplasia. The results of the present study suggest that
GTP possesses anti-skin
tumor-promoting effects, and that the mechanism of such effects may involve inhibition of
tumor promoter-induced epidermal
ornithine decarboxylase,
cyclooxygenase and
lipoxygenase activities,
edema, and
hyperplasia. Further studies are in progress to define which component present in
GTP is responsible for its anti-skin
tumor-promoting effects.