Angoline: a selective IL-6/STAT3 signaling pathway inhibitor isolated from Zanthoxylum nitidum.

Abstract

STAT3 signaling pathway is an important target for human cancer therapy. Thus, the identification of small-molecules that target STAT3 signaling will be of great interests in the development of anticancer agents. The aim of this study was to identify novel inhibitors of STAT3 pathway from the roots of Zanthoxylum nitidum (Roxb.) DC. The bioassay-guided fractionation of MeOH extract of Z. nitidum using a STAT3-responsive gene reporter assay led to the isolation of angoline (1) as a potent and selective inhibitor of the STAT3 signaling pathway (IC50=11.56 μM). Angoline inhibited STAT3 phosphorylation and its target gene expression and consequently induced growth inhibition of human cancer cells with constitutively activated STAT3 (IC50=3.14-4.72 μM). This work provided a novel lead for the development of anti-cancer agents targeting the STAT3 signaling pathway.

• Authors: Jiawei Liu, Qing Zhang, Yushan Ye, Wuguo Li, Junxin Qiu, Jingli Liu, Ruoting Zhan, Weiwen Chen, Qiang Yu
• Journal: Phytomedicine : international journal of phytotherapy and phytopharmacology (Phytomedicine) 2014 Jul-Aug Vol. 21 Issue 8-9 Pg. 1088-91 ISSN: 1618-095X [Electronic] Germany
• PMID: 24863036 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier GmbH. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• IL6 protein, human
• Interleukin-6
• Phenanthridines
• Plant Extracts
• STAT3 Transcription Factor
• STAT3 protein, human
• angoline

Topics

• Antineoplastic Agents, Phytogenic (chemistry, isolation & purification, pharmacology)
• Apoptosis (drug effects)
• Cell Proliferation (drug effects)
• Genes, Reporter
• Hep G2 Cells
• Humans
• Inhibitory Concentration 50
• Interleukin-6 (genetics, metabolism)
• Phenanthridines (chemistry, isolation & purification, pharmacology)
• Phosphorylation (drug effects)
• Plant Extracts (chemistry, isolation & purification, pharmacology)
• Plant Roots (chemistry)
• STAT3 Transcription Factor (genetics, metabolism)
• Signal Transduction (drug effects)
• Zanthoxylum (chemistry)