Quercetin and EGCG Exhibit Chemopreventive Effects in Cholangiocarcinoma Cells via Suppression of JAK/STAT Signaling Pathway
Article first published online: 30 AUG 2013
Copyright © 2013 John Wiley & Sons, Ltd.
Volume 28, Issue 6, pages 841–848, June 2014
How to Cite
Senggunprai, L., Kukongviriyapan, V., Prawan, A. and Kukongviriyapan, U. (2014), Quercetin and EGCG Exhibit Chemopreventive Effects in Cholangiocarcinoma Cells via Suppression of JAK/STAT Signaling Pathway. Phytother. Res., 28: 841–848. doi: 10.1002/ptr.5061
- Issue published online: 6 JUN 2014
- Article first published online: 30 AUG 2013
- Manuscript Accepted: 4 AUG 2013
- Manuscript Revised: 3 JUN 2013
- Manuscript Received: 5 OCT 2012
- Thailand Research Fund. Grant Number: Grant No. MRG5480011
Quercetin and epigallocatechin-3-gallate (EGCG) are dietary phytochemicals with antiinflammatory and antitumor effects. In the present study, we examined the effects of these two compounds on Janus-like kinase (JAK)/signal transduction and transcription (STAT) pathway of cholangiocarcinoma (CCA) cells, because CCA is one of the aggressive cancers with very poor prognosis and JAK/STAT pathway is critically important in inflammation and carcinogenesis. The results showed that the JAK/STAT pathway activation by proinflammatory cytokine interleukin-6 and interferon-γ in CCA cells was suppressed by pretreatment with quercetin and EGCG, evidently by a decrease of the elevated phosphorylated-STAT1 and STAT3 proteins in a dose-dependent manner. The cytokine-mediated up-regulation of inducible nitric oxide synthase (iNOS) and intercellular adhesion molecule-1 (ICAM-1) via JAK/STAT cascade was abolished by both quercetin and EGCG pretreatment. Moreover, these flavonoids also could inhibit growth and cytokine-induced migration of CCA cells. Pretreatment with specific JAK inhibitors, AG490 and piceatannol, abolished cytokine-induced iNOS and ICAM-1 expression. These results demonstrate beneficial effects of quercetin and EGCG in the suppression of JAK/STAT cascade of CCA cells. Quercetin and EGCG would be potentially useful as cancer chemopreventive agents against CCA. Copyright © 2013 John Wiley & Sons, Ltd.