Quercetin and EGCG exhibit chemopreventive effects in cholangiocarcinoma cells via suppression of JAK/STAT signaling pathway.

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.

• Authors: Laddawan Senggunprai, Veerapol Kukongviriyapan, Auemduan Prawan, Upa Kukongviriyapan
• Journal: Phytotherapy research : PTR (Phytother Res) Vol. 28 Issue 6 Pg. 841-8 (Jun 2014) ISSN: 1099-1573 [Electronic] England
• PMID: 24038588 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 John Wiley & Sons, Ltd.

Chemical References

• ICAM1 protein, human
• IFNG protein, human
• IL6 protein, human
• Interleukin-6
• STAT1 Transcription Factor
• STAT1 protein, human
• STAT3 Transcription Factor
• STAT3 protein, human
• STAT5 Transcription Factor
• STAT5A protein, human
• Tumor Suppressor Proteins
• Intercellular Adhesion Molecule-1
• Interferon-gamma
• Catechin
• Quercetin
• epigallocatechin gallate
• NOS2 protein, human
• Nitric Oxide Synthase Type II
• JAK1 protein, human
• JAK2 protein, human
• Janus Kinase 1
• Janus Kinase 2

Topics

• Bile Duct Neoplasms (metabolism, pathology)
• Bile Ducts, Intrahepatic (pathology)
• Catechin (analogs & derivatives, pharmacology)
• Cell Line, Tumor
• Cholangiocarcinoma (metabolism, pathology)
• Humans
• Intercellular Adhesion Molecule-1 (metabolism)
• Interferon-gamma (metabolism)
• Interleukin-6 (metabolism)
• Janus Kinase 1 (metabolism)
• Janus Kinase 2 (metabolism)
• Nitric Oxide Synthase Type II (metabolism)
• Phosphorylation (drug effects)
• Quercetin (pharmacology)
• STAT1 Transcription Factor (metabolism)
• STAT3 Transcription Factor (metabolism)
• STAT5 Transcription Factor
• Signal Transduction (drug effects)
• Tumor Suppressor Proteins