13-cis-retinoic acid induces apoptosis by modulating caspase-3, bcl-2, and p53 gene expression and regulates the activation of transcription factors in B16F-10 melanoma cells.
Cancer prevention using natural products has become an integral part of cancer control. In this study we investigated the effect of 13-cis-retinoic acid 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 13-cis-retinoic acid showed the presence of apoptotic bodies and induced DNA fragmentation. 13-cis-retinoic acid treatment also showed an inhibitory effect on bcl-2 expression and upregulated p53 and caspase-3 gene expression in B16F-10 melanoma cells. The study also reveals that 13-cis-retinoic acid 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-kappaB, 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 13-cis-retinoic acid effectively induces apoptosis in B16F-10 melanoma cells and this compound has the potential as either a therapeutic or chemotherapeutic agent against melanoma.
Guruvayoorappan
Chandrasekharan
C
Department of Immunology, Amala Cancer Research Centre, Amala Nagar, Thrissur-680555, Kerala State, India.
Pradeep
Chaluvally Raghavan
CR
Kuttan
Girija
G
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D015474:Isotretinoin / Q000494:pharmacology*; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
D000970:Antineoplastic Agents; D016207:Cytokines; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C505409:Casp3 protein, mouse; D053148:Caspase 3; D015474:Isotretinoin