Arctigenin inhibits STAT3 and exhibits anticancer potential in human triple-negative breast cancer therapy

// Tingting Feng 1, 2, * , Wei Cao 3, * , Wanxiang Shen 4 , Liang Zhang 1 , Xinsheng Gu 5 , Yang Guo 5 , Hsiang-i Tsai 4 , Xuewen Liu 1 , Jian Li 5 , Jingxuan Zhang 5 , Shan Li 5 , Fuyun Wu 5 , Ying Liu 1, 5 1 Laboratory of Molecular Target Therapy of Cancer, Institute of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, China 2 School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, China 3 MOE Key Laboratory of Industrial Fermentation Microbiology, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China 4 Graduate School at Shenzhen, Tsinghua University, Shenzhen, Guangdong 518055, China 5 School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, China * These authors contributed equally to this work Correspondence to: Ying Liu, email: ying_liu1002@163.com Keywords: arctigenin, STAT3, triple-negative breast cancers, computational docking, taxotere Received: May 05, 2016      Accepted: November 11, 2016      Published: November 16, 2016 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.