Tea polyphenolic constituents induce apoptosis in
cancer cells but not in normal cells. To study the mechanism of this selective effect, we used the
ornithine decarboxylase (ODC)/Ras double transgenic mouse model that develops spontaneous skin
tumors due to over-expression of ODC and a v-Ha-ras transgene. Administration of the
green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) in the
drinking water significantly decreased both
tumor number and total
tumor burden compared with untreated ODC/Ras mice without decreasing the elevated
polyamine levels present in the ODC/Ras mice. EGCG selectively decreased both proliferation and survival of primary cultures of ODC over-expressing transgenic keratinocytes but not keratinocytes from normal littermates nor ras-infected keratinocytes. This decreased survival was due to EGCG-induced apoptosis and not terminal differentiation. Moreover, in skin from EGCG-treated ODC transgenic mice,
caspase 3 (active form) was detected only in epidermal cells that possess very high levels of ODC
protein. Since most transformed cells and
tumor tissue possess higher levels of
polyamines compared with normal cells or tissue, our data suggest that the elevated levels of
polyamines in
tumor cells sensitize them to EGCG-induced apoptosis. These results suggest that EGCG may be an effective chemopreventive agent in individuals with early, pre-neoplastic stages of
cancer having higher levels of
polyamines.