title: 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.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. Electronic address: jiawei.liu@ymail.com.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
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.
authors.forename: Yushan
authors.initials: Y
authors.lastname: Ye
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.
authors.forename: Wuguo
authors.initials: W
authors.lastname: Li
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.
authors.forename: Junxin
authors.initials: J
authors.lastname: Qiu
authors.affiliation: Department of Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People's Republic of China.
authors.forename: Jingli
authors.initials: J
authors.lastname: Liu
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.
authors.forename: Ruoting
authors.initials: R
authors.lastname: Zhan
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.
authors.forename: Weiwen
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People's Republic of China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Yu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D017930:Genes, Reporter; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D010617:Phenanthridines / 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 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D032106:Zanthoxylum / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C508600:IL6 protein, human; D015850:Interleukin-6; D010617:Phenanthridines; D010936:Plant Extracts; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C113966:angoline
keywords: Angoline; Inhibitor; STAT3 signaling pathway; Zanthoxylum nitidum