Capsaicin inhibits the IL-6/STAT3 pathway by depleting intracellular gp130 pools through endoplasmic reticulum stress.
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.
Lee
Hyun Kyoung
HK
Department of Physiology, College of Medicine, Dong-A University, Seo-Gu, Busan, South Korea.
Seo
In Ae
IA
Shin
Yoon Kyung
YK
Park
Ji Wook
JW
Suh
Duk Joon
DJ
Park
Hwan Tae
HT
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
D000970:Antineoplastic Agents; D002211:Capsaicin; D050822:Cytokine Receptor gp130; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D000093242:Interleukin-6 Inhibitors