title: Wogonoside inhibits angiogenesis in breast cancer via suppressing Wnt/β-catenin pathway.
abstract: Wogonoside, a main flavonoid component derived from the root of Scutellaria baicalensis Georgi, has been reported to have anti-angiogenesis and anti-leukemia activities. However, whether it can inhibit tumor angiogenesis is unclear. In this study, we investigate the inhibitory effect of wogonoside on angiogenesis in breast cancer and its underlying mechanisms. ELISA assay shows that wogonoside (25, 50, and 100 µM) decreases the secretion of VEGF in MCF-7 cells by 30.0%, 35.4%, and 40.1%, respectively. We find it inhibits angiogenesis induced by the conditioned media from MCF-7 cells in vitro and in vivo by migration, tube formation, rat aortic ring, and chicken chorioallantoic membrane (CAM) assay. Meanwhile, wogonoside can inhibit the growth and angiogenesis of MCF-7 cells xenografts in nude mice. The reduction of tumor weight can be found both in wogonoside (80 mg/kg) and bevacizumab (20 mg/kg) treated group, and the tumor inhibition rate is 42.1% and 48.7%, respectively. In addition, mechanistic studies demonstrate that wogonoside suppresses the activation of Wnt/β-catenin pathway in MCF-7 cells. Wogonoside (100 µM) decreases the intracellular level of Wnt3a, increases the expression of GSK-3β, AXIN, and promotes the phosphorylation of β-catenin for proteasome degradation significantly. Furthermore, the nuclear accumulation of β-catenin and the DNA-binding activity of β-catenin/TCF/Lef complex are inhibited by 49.2% and 28.7%, respectively, when treated with 100 µM wogonoside. Taken together, our findings demonstrate that wogonoside is a potential inhibitor of tumor angiogenesis and can be developed as a therapeutic agent for breast cancer. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Jiangsu Key Laboratory of Carcinogenesis and Intervention, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Jiangsu Key Laboratory of Carcinogenesis and Intervention, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhao
authors.affiliation: Jiangsu Key Laboratory of Carcinogenesis and Intervention, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Jiangsu Key Laboratory of Carcinogenesis and Intervention, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Jiangsu Key Laboratory of Carcinogenesis and Intervention, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Xuwei
authors.initials: X
authors.lastname: Luo
authors.affiliation: Jiangsu Key Laboratory of Carcinogenesis and Intervention, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Xiaorui
authors.initials: X
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory of Carcinogenesis and Intervention, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Libin
authors.initials: L
authors.lastname: Wei
authors.affiliation: Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Qidong
authors.initials: Q
authors.lastname: You
authors.affiliation: Jiangsu Key Laboratory of Carcinogenesis and Intervention, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People's Republic of China. anticancer_drug@163.com.
authors.forename: Qinglong
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Jiangsu Key Laboratory of Carcinogenesis and Intervention, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People's Republic of China. luna555@163.com.
authors.forename: Na
authors.initials: N
authors.lastname: Lu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D044950:Flavanones / Q000008:administration & dosage* / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005960:Glucosides / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D044950:Flavanones; D005960:Glucosides; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C473995:wogonoside
keywords: Wnt/β-catenin; angiogenesis; breast cancer; wogonoside