Kansuinine A and Kansuinine B from Euphorbia kansui L. inhibit IL-6-induced Stat3 activation.
The current study was performed to examine the mechanisms underlying the potential effects of E. KANSUI on IL-6-induced cellular signaling in human hepatoma cells. We found that two diterpenoids, kansuinine A and B, from E. KANSUI have an inhibitory effect on IL-6-induced Stat3 activation by activating ERK1/2. Inhibition of MEK significantly blocked the effects of kansuinine A and B on IL-6-induced Stat3 activation and tyrosine phosphorylation. These results suggest that blocking of IL-6-induced signal transduction is partially due to the sustained activation of ERK1/2 by kansuinine A and B, which in turn results in an increase of Stat3 serine phosphorylation and SOCS-3 expression. Treatment with kansuinine A and B represents a novel method to block these IL-6-induced effects.
Chang
Jong Sun
JS
Korea Research Institute of Bioscience and Biotechnology, Jeongeup-si, Korea.
Lee
Seung Woong
SW
Park
Mi Hye
MH
Kim
Myo Sun
MS
Hudson
Barry I
BI
Park
Su-Jin
SJ
Lee
Woo Song
WS
Rho
Mun-Chual
MC
D002478:Cells, Cultured; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D028481:Euphorbia / Q000737:chemistry*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects*; D000093242:Interleukin-6 Inhibitors
D004224:Diterpenes; D048049:Extracellular Signal-Regulated MAP Kinases; D050796:STAT3 Transcription Factor; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D000093242:Interleukin-6 Inhibitors; C106644:SOCS3 protein, human; C494086:STAT3 protein, human; C470413:kansuinin B; C104302:kansuinin A