Abstract
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.
MeSH terms
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Activating Transcription Factor 2
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Alkaloids / pharmacology*
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Benzodioxoles
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Cell Line, Tumor
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Cell Nucleus / drug effects
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Cell Nucleus / metabolism
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Cell Proliferation / drug effects
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Collagen / chemistry
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Cyclic AMP Response Element-Binding Protein / antagonists & inhibitors
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Cyclic AMP Response Element-Binding Protein / genetics*
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Cytokines / biosynthesis
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Cytokines / genetics*
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Enzyme-Linked Immunosorbent Assay
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Gelatin
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Gene Expression / drug effects
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Genes, fos / drug effects*
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Humans
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Matrix Metalloproteinases / genetics
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Matrix Metalloproteinases / metabolism
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Melanoma, Experimental / metabolism*
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NF-kappa B / antagonists & inhibitors
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NF-kappa B / genetics*
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Piperidines / pharmacology*
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Polyunsaturated Alkamides
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RNA / biosynthesis
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RNA / genetics
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RNA / isolation & purification
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Reverse Transcriptase Polymerase Chain Reaction
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Transcription Factors / antagonists & inhibitors
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Transcription Factors / genetics*
Substances
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ATF2 protein, human
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Activating Transcription Factor 2
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Alkaloids
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Benzodioxoles
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Cyclic AMP Response Element-Binding Protein
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Cytokines
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NF-kappa B
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Piperidines
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Polyunsaturated Alkamides
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Transcription Factors
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RNA
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Gelatin
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Collagen
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Matrix Metalloproteinases
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piperine