Regulation of Constitutive and Induced NF-κB Activation in Malignant Melanoma Cells by Capsaicin Modulates Interleukin-8 Production and Cell Proliferation

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Abstract
In the present study, we demonstrate that upregulation of interleukin-1β(IL-1β)-mediated and tumor necrosis factor-α (TNF-α)-mediated IL-8 expression in human malignant melanoma cells is modulated by the activation of nuclear factor-κB (NF-κB). Addition of capsaicin (8-methyl-N-vanillyl-6-nonenamide), a known inhibitor of NF-κB, resulted in the inhibition of constitutive as well as IL-1β-induced and TNF-α-induced IL-8 expression in melanoma cells. The inhibition of IL-8 expression was dependent on the concentration of capsaicin and duration of treatment. Further, electrophoretic mobility shift assay (EMSA) of nuclear extracts from melanoma cells showed a constitutive activation of NF-κB and activated protein 1 (AP-1), which was upregulated following treatment with IL-1β. Treatment of melanoma cells with capsaicin inhibited activation of constitutive and IL-1β-induced NF-κB, but not AP-1, leading to inhibition of IL-8 expression. Further, downregulation of IL-8 expression in capsaicin-treated melanoma cells resulted in inhibition of in vitro cell proliferation. These results demonstrate that constitutive and induced NF-κB activation regulates IL-8 expression in melanoma cells. Downregulation of constitutive and induced NF-κB activation in malignant melanoma cells leads to inhibition of IL-8 production and in vitro cell proliferation.