Oleanolic Acid Induces Apoptosis by Modulating p53, BAX, Bcl-2, and Caspase-3 Gene Expression, and Regulates the Activation of Transcription Factors and Cytokine Profile in B16F-10 Melanoma Cells

The objective of this study was to assess the effect of OA, a triterpene on inducing apoptosis in B16F-10 melanoma cells. Treatment of B16F-10 cells with nontoxic concentration of OA showed the presence of apoptotic bodies and induced DNA fragmentation in a dose-depended manner. Cell cycle analysis and TUNEL assay also confirmed the observation. The apoptotic genes p53, BAX, caspase-9, and caspase-3 were found upregulated in oleanolic acid treated cells, whereas the antiapoptotic gene Bcl-2 was downregulated. OA treatment also showed a downregulation of Cyclin D1 expression and upregulated p21 and p27 gene expression in B16F-10 melanoma cells. OA inhibited the activation and nuclear translocation of transcription factors such as NF-kappa B, c-fos, ATF-2, and CREB-1, and also downregulated the production and expression of TNF-alpha, IL-1 beta, IL-6, and GM-CS. These results suggest that OA induces apoptosis through activating the p53-induced caspase-mediated proapoptotic pathway and suppression of the NF-kappa B induced Bcl-2 mediated antiapoptotic pathway.