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

Int Immunopharmacol. 2004 Dec 20;4(14):1795-803. doi: 10.1016/j.intimp.2004.08.005.

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

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

Substances

  • ATF2 protein, human
  • Activating Transcription Factor 2
  • Alkaloids
  • Benzodioxoles
  • Cyclic AMP Response Element-Binding Protein
  • Cytokines
  • NF-kappa B
  • Piperidines
  • Polyunsaturated Alkamides
  • Transcription Factors
  • RNA
  • Gelatin
  • Collagen
  • Matrix Metalloproteinases
  • piperine