title: Vernolide-A, a sesquiterpene lactone from Vernonia cinerea, induces apoptosis in B16F-10 melanoma cells by modulating p53 and caspase-3 gene expressions and regulating NF-κB-mediated bcl-2 activation.
abstract: In this study, we investigated the effect of vernolide-A on the induction of apoptosis as well as its regulatory effect on the activation of transcription factors in B16F-10 melanoma cells. Treatment of B16F-10 cells with nontoxic concentrations of vernolide-A showed the presence of apoptotic bodies and induced DNA fragmentation in a dose-dependent manner. Cell-cycle analysis and TUNEL assays also confirmed the observation. The proapoptotic genes, p53, Bax, caspase-9, and caspase-3, were upregulated in vernolide-A-treated cells, whereas the antiapoptotic gene, Bcl-2, was downregulated. vernolide-A treatment also showed a downregulation of cyclin D1 expression and upregulated p21 and p27 gene expression in B16F-10 melanoma cells. The study also reveals that vernolide-A treatment could alter the production and expression of proinflammatory cytokines and could inhibit the activation and nuclear translocation of p65, p50, and c-Rel subunits of nuclear factor-κB and other transcription factors, such as c-fos, activated transcription factor-2, and cyclic adenosine monophosphate response-element-binding protein in B16F-10 melanoma cells. These results suggest that vernolide-A induces apoptosis via activation of p53-induced, caspase-3-mediated proapoptotic signaling and suppression of NF-κB-induced, bcl-2-mediated survival signaling.
authors.affiliation: Amala Cancer Research Center, Amala Nagar, Thrissur, India.
authors.forename: Poyil
authors.initials: P
authors.lastname: Pratheeshkumar
authors.forename: Girija
authors.initials: G
authors.lastname: Kuttan
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000235:genetics*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D007783:Lactones / Q000302:isolation & purification / Q000494:pharmacology*; D008546:Melanoma, Experimental; D051379:Mice; D015394:Molecular Structure; D016328:NF-kappa B / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D035741:Vernonia / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016207:Cytokines; D007783:Lactones; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D012717:Sesquiterpenes; D016159:Tumor Suppressor Protein p53; C558651:vernolide-A; C505409:Casp3 protein, mouse; D053148:Caspase 3