Phloretin-induced apoptosis in B16 melanoma 4A5 cells and HL60 human leukemia cells

The dihydrochalcone phloretin induced apoptosis in B16 mouse melanoma 4A5 c ells and HL60 human leukemia cells. Phloretin was suggested to induce apopt osis in B16 cells mainly through the inhibition of glucose transmembrane tr ansport. The phloretin-induced apoptosis in B16 tells was inhibited by acti nomycin D, Ac-YVAD-CHO caspase-1-like inhibitor, and Ac-DEVD-CHO caspase-3- like inhibitor. During the induction of apoptosis by phloretin, the express ion of Bar protein in B16 cells increased and the levels of p53, Bcl-2, and Bcl-X-L proteins did not change. Our results suggested that phloretin indu ced apoptosis through the promotion of Bar protein expression and caspases activation. On the other hand, phloretin may induce apoptosis in HL60 cells through the inhibition of protein kinase C activity because phloretin inhi bited protein kinase C activity in HL60 cells more than that in B16 cells. The phloretin induced-apoptosis in HL60 cells was not inhibited by actinomy cin D and the caspase-1-like inhibitor, but slightly inhibited by the caspa se3-like inhibitor. Phloretin reduced the level of caspase 3 protein in HL6 0 cells, but not the level of the Bcl-2 protein. Phloretin did not increase the level of Bar protein. Phloretin was suggested to induce apoptosis in H L60 cells through the inhibition of protein kinase C activity, followed by the pathway, which is different from that in B16 cells.