title: Arctigenin inhibits STAT3 and exhibits anticancer potential in human triple-negative breast cancer therapy.
abstract: Triple-negative breast cancers (TNBCs) are the most aggressive and hard-to-treat breast tumors with poor prognosis, and exploration for novel therapeutic drugs is impending. Arctigenin (Atn), a bioactive lignan isolated from seeds of Arctium lappa L, has been reported to inhibit many cancer types; however, the effect of Atn on TNBC remains unclear. In this study, we demonstrated that Atn decreased proliferation, and induced apoptosis in TNBC cells. Furthermore, we explored the underlying mechanism of Atn inhibition on TNBC cells. Computational docking and affinity assay showed that Atn bound to the SH2 domain of STAT3. Atn inhibited STAT3 binding to genomic DNA by disrupting hydrogen bond linking between DNA and STAT3. In addition, Atn augmented Taxotere®-induced TNBC cell cytotoxicity. TNBC xenograft tests also confirmed the antitumor effect of Atn in vivo. These characteristics render Atn as a promising candidate drug for further development and for designing new effective STAT3 inhibitors.
authors.affiliation: Laboratory of Molecular Target Therapy of Cancer, Institute of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, China.|School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Feng
authors.affiliation: MOE Key Laboratory of Industrial Fermentation Microbiology, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
authors.affiliation: Graduate School at Shenzhen, Tsinghua University, Shenzhen, Guangdong 518055, China.
authors.forename: Wanxiang
authors.initials: W
authors.lastname: Shen
authors.affiliation: Laboratory of Molecular Target Therapy of Cancer, Institute of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, China.
authors.forename: Xinsheng
authors.initials: X
authors.lastname: Gu
authors.affiliation: School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Graduate School at Shenzhen, Tsinghua University, Shenzhen, Guangdong 518055, China.
authors.forename: Hsiang-I
authors.initials: HI
authors.lastname: Tsai
authors.affiliation: Laboratory of Molecular Target Therapy of Cancer, Institute of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, China.
authors.forename: Xuewen
authors.initials: X
authors.lastname: Liu
authors.affiliation: School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, China.
authors.forename: Jingxuan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Li
authors.affiliation: School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, China.
authors.forename: Fuyun
authors.initials: F
authors.lastname: Wu
authors.affiliation: Laboratory of Molecular Target Therapy of Cancer, Institute of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, China.|School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D031170:Arctium / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D000077143:Docetaxel; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D005202:Asia, Eastern; D005260:Female; D005455:Fluorescent Antibody Technique; D005663:Furans / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006860:Hydrogen Bonding / Q000187:drug effects; D017705:Lignans / Q000494:pharmacology* / Q000627:therapeutic use; D008819:Mice, Nude; D062105:Molecular Docking Simulation; D010946:Plants, Medicinal / Q000737:chemistry; D000072417:Protein Domains; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D043823:Taxoids / Q000494:pharmacology*; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D005663:Furans; D017705:Lignans; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D043823:Taxoids; D000077143:Docetaxel; D004247:DNA; C071942:arctigenin
keywords: STAT3; arctigenin; computational docking; taxotere; triple-negative breast cancers