Ursolic acid induces apoptosis by activating p53 and caspase-3 gene expressions and suppressing NF-κB mediated activation of bcl-2 in B16F-10 melanoma cells

Abstract

The objective of this study was to assess the effect of ursolic acid, a triterpene on inducing apoptosis in B16F-10 melanoma cells. Treatment of B16F-10 cells with nontoxic concentration of ursolic acid showed the presence of apoptotic bodies and induced DNA fragmentation in a dose depended manner. The apoptotic genes p53 and caspase-3 were found to be upregulated while the anti-apoptotic gene bcl-2 was down regulated in ursolic acid treated cells. The transcription factors NF-κBp65, NF-κBp50, NF-κBc-Rel, c-FOS, ATF-2 and CREB-1 were found to be inhibited significantly ( p < 0.001) in ursolic acid treated cells compared to untreated control. The pro-inflammatory cytokine production and gene expression of TNF-α, IL-1β, IL-6 and GM-CSF were down regulated in ursolic acid treated cells compared to nontreated B16F-10 metastatic melanoma cells. All these results demonstrate that ursolic acid induce apoptosis via inhibition of NF-κB induced bcl-2 mediated anti-apoptotic pathway and subsequent activation of p53 mediated and TNF-α induced caspase-3 mediated pro-apoptotic pathways.