Quercetin and EGCG Exhibit Chemopreventive Effects in Cholangiocarcinoma Cells via Suppression of JAK/STAT Signaling Pathway
- 30 August 2013
- journal article
- research article
- Published by Wiley in Phytotherapy Research
- Vol. 28 (6), 841-848
- https://doi.org/10.1002/ptr.5061
Abstract
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.Keywords
Funding Information
- Thailand Research Fund (Grant No. MRG5480011)
This publication has 32 references indexed in Scilit:
- Dicoumarol enhances gemcitabine-induced cytotoxicity in high NQO1-expressing cholangiocarcinoma cellsWorld Journal of Gastroenterology, 2010
- Flavonoids as anti-inflammatory agents: implications in cancer and cardiovascular diseaseInflammation Research, 2009
- Silibinin inhibits cytokine-induced signaling cascades and down-regulates inducible nitric oxide synthase in human lung carcinoma A549 cellsMolecular Cancer Therapeutics, 2008
- STAT3 and STAT1 mediate IL-11–dependent and inflammation-associated gastric tumorigenesis in gp130 receptor mutant miceJCI Insight, 2008
- Cyclooxygenase-2-Dependent Activation of Signal Transducer and Activator of Transcription 3 by Interleukin-6 in Non–Small Cell Lung CancerClinical Cancer Research, 2005
- Comparison of gene expression in HCT116 treatment derivatives generated by two different 5-fluorouracil exposure protocolsMolecular Cancer, 2004
- Mechanism-based in vitro screening of potential cancer chemopreventive agentsMutation Research - Reviews in Mutation Research, 2003
- Piceatannol Inhibits TNF-Induced NF-κB Activation and NF-κB-Mediated Gene Expression Through Suppression of IκBα Kinase and p65 PhosphorylationThe Journal of Immunology, 2002
- Inhibition of growth hormone action in models of inflammationAmerican Journal of Physiology-Cell Physiology, 2000
- STATs and Gene RegulationScience, 1997