Myricetin inhibits Akt survival signaling and induces Bad‐mediated apoptosis in a low dose ultraviolet (UV)‐B‐irradiated HaCaT human immortalized keratinocytes

Abstract

Deregulation of cell survival pathways and resistance to apoptosis are generally accepted as crucial aspects of tumorigenesis. As in many tumors, increasing occurrence of human skin cancer and other conflicting effects of solar ultraviolet radiation enhance the demand for novel chemoprevention agents. Myricetin, a naturally occurring phytochemical, is potent in anti‐cancer promoting activity and affords to the chemopreventive potential of several healthy‐foods. We demonstrate that myricetin inhibits Akt activity to induce apoptosis in a low dose UVB‐irradiated keratinocytes. Treatment of UVB‐irradiated HaCaT cells with an apoptosis‐inducing concentration of myricetin resulted in a decrease in phosphorylation of Akt leading to inhibition of its kinase activity, followed by a decrease in phosphorylation of Bad (a pro‐apoptotic protein), a direct target of Akt in signaling pathway. Comparable to these results, myricetin promoted mitochondrial translocation of Bad, loss of the mitochondrial membrane potential, and release of the mitochondrial apoptotic proteins. In addition, myricetin‐induced apoptosis in UVB‐irradiated cells was attenuated in the presence of caspase inhibitors. Together, these results indicate that myricetin might take on potent chemopreventive activity by targeting the Akt‐mediated apoptotic signaling axis in UVB‐induced skin carcinogenesis.