Elevated polyamines lead to selective induction of apoptosis and inhibition of tumorigenesis by (-)-epigallocatechin-3-gallate (EGCG) in ODC/Ras transgenic mice

Carcinogenesis
Barry PaulSusan K Gilmour

Abstract

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 sensi...Continue Reading

Citations

Dec 25, 2007·Antioxidants & Redox Signaling·Naghma KhanHasan Mukhtar
Aug 29, 2007·Acta Pharmacologica Sinica·Imtiaz A SiddiquiHasan Mukhtar
Feb 13, 2008·Photochemistry and Photobiology·Vaqar M AdhamiFarrukh Afaq
Oct 6, 2005·Journal of Cellular and Molecular Medicine·Nikolaus Seiler, Francis Raul
Apr 26, 2008·Molecular Nutrition & Food Research·Sonia Ramos
Dec 4, 2009·Amino Acids·Esther MelgarejoMiguel Angel Medina
Sep 10, 2005·Apoptosis : an International Journal on Programmed Cell Death·M SchillerH M Lorenz
Aug 15, 2014·International Journal of Oncology·Michele LinsalataFrancesco Russo

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