title: Capsaicin inhibits the IL-6/STAT3 pathway by depleting intracellular gp130 pools through endoplasmic reticulum stress.
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.
authors.affiliation: Department of Physiology, College of Medicine, Dong-A University, Seo-Gu, Busan, South Korea.
authors.forename: Hyun Kyoung
authors.initials: HK
authors.lastname: Lee
authors.forename: In Ae
authors.initials: IA
authors.lastname: Seo
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Shin
authors.forename: Ji Wook
authors.initials: JW
authors.lastname: Park
authors.forename: Duk Joon
authors.initials: DJ
authors.lastname: Suh
authors.forename: Hwan Tae
authors.initials: HT
authors.lastname: Park
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D050822:Cytokine Receptor gp130 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D015536:Down-Regulation; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects; D051381:Rats; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction; D000093242:Interleukin-6 Inhibitors
chemical_list: D000970:Antineoplastic Agents; D002211:Capsaicin; D050822:Cytokine Receptor gp130; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D000093242:Interleukin-6 Inhibitors