Piperine is a potent inhibitor of nuclear factor-kappaB (NF-kappaB), c-Fos, CREB, ATF-2 and proinflammatory cytokine gene expression in B16F-10 melanoma cells.
Immune regulation, induction of various inflammatory and growth regulatory genes such as IL-1beta, IL-6, TNF-alpha and GM-CSF require activation of transcription factors such as nuclear factor-kappaB (NF-kappaB), activated transcription factor (ATF-2), c-Fos and cAMP response element-binding protein (CREB). Untreated B16F-10 cells produce very high amount of proinflammatory cytokines such as IL-1beta, IL-6, TNF-alpha and GM-CSF. Piperine treatment significantly reduced the above proinflammatory cytokines. We also found that piperine could reduce the expression of IL-1beta, IL-6, TNF-alpha, GM-CSF and IL-12p40 genes. Piperine at a concentration of 2.5, 5 and 10 microg/ml inhibited the collagen matrix invasion of B16F-10 melanoma cells in a dose-dependent manner. Piperine could inhibit the matrix metalloproteinase production which was demonstrated by zymographic analysis. We found that the nuclear translocation of p65, p50, c-Rel subunits of NF-kappaB and other transcription factors such as ATF-2, c-Fos and CREB were inhibited by the treatment of piperine.
Pradeep
C R
CR
Department of Immunology, Amala Cancer Research Centre, Amala Nagar, Thrissur, Kerala 680 555, India.
Kuttan
G
G
D051698:Activating Transcription Factor 2; D000470:Alkaloids / Q000494:pharmacology*; D052117:Benzodioxoles; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000737:chemistry; D017362:Cyclic AMP Response Element-Binding Protein / Q000037:antagonists & inhibitors / Q000235:genetics*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005780:Gelatin; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects*; D006801:Humans; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D008546:Melanoma, Experimental / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics*; D010880:Piperidines / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides; D012313:RNA / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics*
C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; D000470:Alkaloids; D052117:Benzodioxoles; D017362:Cyclic AMP Response Element-Binding Protein; D016207:Cytokines; D016328:NF-kappa B; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D014157:Transcription Factors; D012313:RNA; D005780:Gelatin; D003094:Collagen; D020782:Matrix Metalloproteinases; C008922:piperine