title: Amentoflavone stimulates apoptosis in B16F-10 melanoma cells by regulating bcl-2, p53 as well as caspase-3 genes and regulates the nitric oxide as well as proinflammatory cytokine production in B16F-10 melanoma cells, tumor associated macrophages and peritoneal macrophages.
abstract: Polyphenolic compounds present in fruits, vegetables, herbs, roots and leaves act as bioactive components and has been recognized as cancer chemopreventive agents. The present study is focused on the regulatory effect of amentoflavone, a biflavonoid from Biophytum sensitivum on the apoptotic process in B16F-10 melanoma cells as well as nitric oxide (NO) and cytokine production in B16F-10 cells, Tumor associated macrophages (TAMs) and peritoneal macrophages. Amentoflavone at a concentration of 10 microg/mL could significantly (p < 0.001) inhibit NO and proinflammatory cytokine (IL-1beta, IL-6, GM-CSF and TNF-alpha) production in B16F-10 cells, TAMs and peritoneal macrophages. Incubation of B16F-10 cells with amentoflavone showed the presence of apoptotic bodies and induced DNA fragmentation. Furthermore, amentoflavone showed inhibitory effect on bcl-2 expression and upregulated p53 and caspase-3 gene expression in B16F-10 melanoma cells. In conclusion, the observed results suggests that, amentoflavone stimulates apoptosis by regulating bcl-2, Caspase-3 and p53 genes in B16F-10 melanoma cells and regulates nitric oxide and proinflammatory cytokine production in B16F-10 cells, TAMs and peritoneal macrophages.
authors.affiliation: Department of Immunology, Amala Cancer Research Centre, Amala Nagar, Thrissur-680 555, Kerala State, India.
authors.forename: Chandrasekharan
authors.initials: C
authors.lastname: Guruvayoorappan
authors.forename: Girija
authors.initials: G
authors.lastname: Kuttan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D044946:Biflavonoids / Q000494:pharmacology*; D053148:Caspase 3 / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008546:Melanoma, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D044946:Biflavonoids; D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D009566:Nitrates; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D009569:Nitric Oxide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C011164:amentoflavone; D052247:Nitric Oxide Synthase Type II; C505409:Casp3 protein, mouse; D053148:Caspase 3