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.

摘要

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 asNF-kappaB, c-fos, ATF-2, and CREB-1, and also downregulated the production and expression of TNF-alpha, IL-1beta,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-kappaB-nduced Bcl-2-ediated antiapoptotic pathway