Planta Med 2012; 78(14): 1568-1570
DOI: 10.1055/s-0032-1315121
Biological and Pharmacological Activity
Letters
Georg Thieme Verlag KG Stuttgart · New York

Small-molecule STAT3 Signaling Pathway Modulators from Polygonum cuspidatum

Jiawei Liu*
1   Ministry of Education Key Laboratory of Chinese Medicinal Plants Resource from Lingnan, Research Center of Medicinal Plants Resource Science and Engineering, Guangzhou University of Chinese Medicine, Guangzhou, Peopleʼs Republic of China
,
Qing Zhang*
2   Departments of Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, Peopleʼs Republic of China
,
Kaotang Chen
1   Ministry of Education Key Laboratory of Chinese Medicinal Plants Resource from Lingnan, Research Center of Medicinal Plants Resource Science and Engineering, Guangzhou University of Chinese Medicine, Guangzhou, Peopleʼs Republic of China
,
Jingli Liu
2   Departments of Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, Peopleʼs Republic of China
,
Shan Kuang
2   Departments of Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, Peopleʼs Republic of China
,
Weiwen Chen
1   Ministry of Education Key Laboratory of Chinese Medicinal Plants Resource from Lingnan, Research Center of Medicinal Plants Resource Science and Engineering, Guangzhou University of Chinese Medicine, Guangzhou, Peopleʼs Republic of China
,
Qiang Yu
2   Departments of Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, Peopleʼs Republic of China
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Publikationsverlauf

received 18. Januar 2012
revised 20. Juni 2012

accepted 04. Juli 2012

Publikationsdatum:
01. August 2012 (online)

Abstract

Constitutively activated STAT3 plays a pivotal role in oncogenesis and metastasis in many human cancers, and STAT3 has been validated as a novel anticancer drug target. Thus, the identification of small molecules that modulate STAT3 activity could be of great therapeutic importance. The aim of this study was to isolate novel modulators of the STAT3 signaling pathway from the roots of Polygonum cuspidatum by bioassay-guided fractionation using a STAT3 reporter gene assay. 2-Methoxystypandrone (1), as well as three anthraquinones (24), were identified as major active components of P. cuspidatum. Compound 1 demonstrated a potent inhibitory effect on STAT3 activation and significantly inhibited cell proliferation of human breast cancer cells, especially those with constitutively activated STAT3 (IC50 = 2.7–3.1 µM). The SAR analysis of quinone analogues suggested that the phenolic and carbonyl groups are the key structures contributing to their inhibitory activities against the STAT3 signaling.

* These authors contributed equally to this work.


Supporting Information

 
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