title: Small-molecule STAT3 signaling pathway modulators from Polygonum cuspidatum.
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 (2-4), 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.
authors.affiliation: 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, People's Republic of China. jiawei.liu@ymail.com
authors.forename: Jiawei
authors.initials: J
authors.lastname: Liu
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.forename: Kaotang
authors.initials: K
authors.lastname: Chen
authors.forename: Jingli
authors.initials: J
authors.lastname: Liu
authors.forename: Shan
authors.initials: S
authors.lastname: Kuang
authors.forename: Weiwen
authors.initials: W
authors.lastname: Chen
authors.forename: Qiang
authors.initials: Q
authors.lastname: Yu
mesh_terms: D000880:Anthraquinones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001681:Biological Assay; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D045468:Fallopia japonica / Q000737:chemistry*; D005260:Female; D006801:Humans; D008516:Medicine, Chinese Traditional; D009285:Naphthoquinones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: C447630:2-Methoxystypandrone; D000880:Anthraquinones; D009285:Naphthoquinones; D010936:Plant Extracts; D050796:STAT3 Transcription Factor