Ursolic acid induces apoptosis by activating p53 and caspase-3 gene expressions and suppressing NF-kappaB mediated activation of bcl-2 in B16F-10 melanoma cells.
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-kappaBp65, NF-kappaBp50, NF-kappaBc-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-alpha, IL-1beta, 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-kappaB induced bcl-2 mediated anti-apoptotic pathway and subsequent activation of p53 mediated and TNF-alpha induced caspase-3 mediated pro-apoptotic pathways.
Manu
K A
KA
Amala Cancer Research Centre, Amala Nagar, Thrissur-680555, Kerala State, India.
Kuttan
Girija
G
D051698:Activating Transcription Factor 2 / Q000037:antagonists & inhibitors; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics*; D045744:Cell Line, Tumor; D017362:Cyclic AMP Response Element-Binding Protein / Q000037:antagonists & inhibitors; D016207:Cytokines / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D019254:Genes, bcl-2; D016158:Genes, p53; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D014315:Triterpenes / Q000494:pharmacology*; D000097245:Ursolic Acid
D051698:Activating Transcription Factor 2; D053148:Caspase 3; D017362:Cyclic AMP Response Element-Binding Protein; D016207:Cytokines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016328:NF-kappa B; D014315:Triterpenes; D000097245:Ursolic Acid