Capsaicin inhibits the IL-6/STAT3 pathway by depleting intracellular gp130 pools through endoplasmic reticulum stress

Biochem Biophys Res Commun. 2009 May 1;382(2):445-50. doi: 10.1016/j.bbrc.2009.03.046. Epub 2009 Mar 13.

Abstract

Capsaicin has been shown to have anti-carcinogenic effects on various tumor cells through multiple mechanisms. It was recently reported that capsaicin inhibited interleukin-6 (IL-6)-induced activation of signal transducer and activator of transcription 3 (STAT3), an anti-apoptotic transcription factor. Here we demonstrate that capsaicin induced downregulation of the IL-6 receptor gp130 within 2h in glial tumors. The downregulation of gp130 was not caused by enhanced degradation of gp130 or by inhibition of mRNA transcription. The downregulation was attributed to translation inhibition of gp130, which was associated with activation of endoplasmic reticulum (ER) stress. The depletion of the intracellular pool of gp130 by capsaicin and an ER stress inducer led to an immediate loss of the IL-6 response due to the short half-life of membrane localized gp130. These results suggest a novel mechanism for the anti-tumor effect of capsaicin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Capsaicin / pharmacology*
  • Cell Line, Tumor
  • Cytokine Receptor gp130 / antagonists & inhibitors*
  • Cytokine Receptor gp130 / biosynthesis
  • Down-Regulation
  • Endoplasmic Reticulum / drug effects*
  • Endoplasmic Reticulum / metabolism
  • Interleukin-6 / antagonists & inhibitors*
  • Interleukin-6 / metabolism
  • Protein Biosynthesis / drug effects
  • Rats
  • STAT3 Transcription Factor / antagonists & inhibitors*
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction

Substances

  • Antineoplastic Agents
  • Interleukin-6
  • STAT3 Transcription Factor
  • Cytokine Receptor gp130
  • Capsaicin