13-cis-Retinoic Acid Induces Apoptosis by Modulating Caspase-3, bcl-2, and p53 Gene Expression and Regulates the Activation of Transcription Factors in B16F-10 Melanoma Cells

Abstract

Cancer prevention using natural products has become an integral part of cancer control. In this study we investigated the effect of 13-cis-retinoic acid on the induction of apoptosis as well as its regulatory effect on the activation of transcription factors in B16F-10 melanoma cells. Treatment of B16F-10 cells with 13-cis-retinoic acid showed the presence of apoptotic bodies and induced DNA fragmentation. 13-cis-retinoic acid treatment also showed an inhibitory effect on bcl-2 expression and upregulated p53 and caspase-3 gene expression in B16F-10 melanoma cells. The study also reveals that 13-cis-retinoic acid treatment could alter the production and expression of proinflammatory cytokines and could inhibit the activation and nuclear translocation of p65, p50, and c-Rel subunits of nuclear factor-kappaB, and other transcription factors such as c-fos, activated transcription factor-2, and cyclic adenosine monophosphate response element-binding protein in B16F-10 melanoma cells. These results suggest that 13-cis-retinoic acid effectively induces apoptosis in B16F-10 melanoma cells and this compound has the potential as either a therapeutic or chemotherapeutic agent against melanoma.