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.