Punarnavine induces apoptosis in B16F-10 melanoma cells by inhibiting NF-kappaB signaling.
The objective of this study was to assess the effect of Punarnavine, an alkaloid isolated from Boerhaavia diffusa, on apoptosis in B16F-10 melanoma cells. Treatment of B16F-10 melanoma cells with nontoxic concentrations of Punarnvine resulted in the presence of apoptotic bodies and DNA fragmentation in a dose dependent manner. Cell cycle analysis and TUNEL assays also confirmed the observation. The apoptotic genes p53 and caspase-3 were found upregulated in Punarnavine treated cells, whereas the antiapoptotic gene Bcl-2 was downregulated. The inhibited nuclear translocation of NF-kappaBp65, NF-kappaBp50, NF-kappaB-c-Rel, c-Fos, ATF-2 and CREB-1 in Punarnavine treated B16 F-10 cells pointed to suppression of NF-kappaB signaling by Punarnavine. All these results demonstrate that Punarnavine induces apoptosis via activation of p53 induced caspase-3 mediated pro-apoptotic signaling and suppression of NF-kappaB induced Bcl-2 mediated survival signaling.
Manu
Kanjoormana Aryan
KA
Department of Immunology, Amala Cancer Research Centre, Thrissur, Kerala, India. amalacancerresearch@gmail.com
Kuttan
Girija
G
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle; D045744:Cell Line, Tumor; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019254:Genes, bcl-2 / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D020287:In Situ Nick-End Labeling; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
D000470:Alkaloids; D016328:NF-kappa B; C526689:punarnavine; D053148:Caspase 3