Apoptotic effect of Biophytum sensitivum on B16F-10 cells and its regulatory effects on nitric oxide and cytokine production on tumor-associated macrophages.
The present study is part of a large-scale investigation of the antitumor effects of Biophytum sensitivum on B16F-10 melanoma cells. The investigation involved the regulatory effect of B sensitivum on nitric oxide and cytokine production in B16F-10 cells, tumor-associated macrophages, and peritoneal macrophages as well as on the apoptotic process in B16F-10 melanoma cells. B sensitivum at a concentration of 10 microg/mL could significantly (P< .001) inhibit production of nitric oxide and proinflammatory cytokines such as interleukin-1beta, interleukin-6, granulocyte monocyte-colony stimulating factor, and tumor necrosis factor-alpha in B16F-10 cells, tumor-associated macrophages, and peritoneal macrophages. Incubation of B16F-10 cells with B sensitivum showed the presence of apoptotic bodies and induced DNA fragmentation. Furthermore, B sensitivum showed an inhibitory effect on inducible nitric oxide synthase as well as bcl-2 expression, and up-regulated p53 and caspase-3 messenger RNA expression in B16F-10 melanoma cells. The observed results suggest that regulation of proinflammatory cytokine production by tumor cells, tumor-associated macrophages, and resident macrophages accompanied by altered inducible nitric oxide synthase, bcl-2, caspase-3, and p53 messenger RNA expression by B sensitivum methanol extract induces apoptosis in B16F-10 melanoma cells.
Department of Immunology, Amala Cancer Research Centre, Amala Nagar, Thrissur, Kerala, India.
C
C
Guruvayoorappan
Girija
G
Kuttan
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism*; D053938:DNA Fragmentation / Q000187:drug effects; D015870:Gene Expression / 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; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D019684:Magnoliopsida / Q000737:chemistry; D008546:Melanoma, Experimental / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D010936:Plant Extracts / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D009566:Nitrates; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D009569:Nitric Oxide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D052247:Nitric Oxide Synthase Type II; C505409:Casp3 protein, mouse; D053148:Caspase 3