PHLORETIN-INDUCED APOPTOSIS IN B16 MELANOMA 4A5 CELLS BY INHIBITION OF GLUCOSE TRANSMEMBRANE TRANSPORT

Phloretin, a naturally occurring dihydrochalcone, is known to inhibit tumor cell growth in vitro and in vivo, To clarify the anti-tumor effe cts of phloretin, its apoptosis-inducing effects in B16 melanoma 4A5 c ells were examined. Phloretin induced the internucleosomal DNA fragmen tation typical of apoptosis in B16 melanoma cells. The addition of ext racellular glucose remarkably inhibited the phloretin-induced apoptosi s in the cells. When apoptosis was strongly induced in the B16 cells b y phloretin, protein kinase C activity was inhibited in the cells. Our results suggest that phloretin induced apoptosis in B16 melanoma 4A5 cells mainly through the inhibition of glucose transmembrane transport . Inhibition of protein kinase C activity by phloretin probably promot es the ratio of apoptotic cells in the cells. (C) 1997 Elsevier Scienc e ireland Ltd.