Regulation of constitutive and induced NF-κB activation in malignant melanoma cells by capsaicin modulates interleukin-8 production and cell proliferation

Prabhudas S. Patel, Michelle L. Varney, Bhavana J Dave, Rakesh K Singh

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33 Citations (Scopus)

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-1beta;-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-1b. 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-kB activation in malignant melanoma cells leads to inhibition of IL-8 production and in vitro cell proliferation.

Original languageEnglish (US)
Pages (from-to)427-435
Number of pages9
JournalJournal of Interferon and Cytokine Research
Volume22
Issue number4
DOIs
StatePublished - Jun 11 2002

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Capsaicin
Interleukin-8
Melanoma
Cell Proliferation
Interleukin-1
Down-Regulation
Tumor Necrosis Factor-alpha
NF-kappa B
Electrophoretic Mobility Shift Assay
Cell Extracts
Proteins
Up-Regulation

ASJC Scopus subject areas

  • Immunology
  • Cell Biology
  • Virology

Cite this

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title = "Regulation of constitutive and induced NF-κB activation in malignant melanoma cells by capsaicin modulates interleukin-8 production and cell proliferation",
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-1beta;-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-1b. 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-kB activation in malignant melanoma cells leads to inhibition of IL-8 production and in vitro cell proliferation.",
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T1 - Regulation of constitutive and induced NF-κB activation in malignant melanoma cells by capsaicin modulates interleukin-8 production and cell proliferation

AU - Patel, Prabhudas S.

AU - Varney, Michelle L.

AU - Dave, Bhavana J

AU - Singh, Rakesh K

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N2 - 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-1beta;-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-1b. 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-kB activation in malignant melanoma cells leads to inhibition of IL-8 production and in vitro cell proliferation.

AB - 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-1beta;-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-1b. 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-kB activation in malignant melanoma cells leads to inhibition of IL-8 production and in vitro cell proliferation.

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