title: Raddeanin A, a triterpenoid saponin isolated from Anemone raddeana, suppresses the angiogenesis and growth of human colorectal tumor by inhibiting VEGFR2 signaling.
abstract: Raddeanin A (RA) is an active triterpenoid saponin from a traditional Chinese medicinal herb, Anemone raddeana Regel. It was previously reported that RA possessed attractive antitumor activity through inhibiting proliferation and inducing apoptosis of multiple cancer cells. However, whether RA can inhibit angiogenesis, an essential step in cancer development, remains unknown. In this study, we found that RA could significantly inhibit human umbilical vein endothelial cell (HUVEC) proliferation, motility, migration, and tube formation. RA also dramatically reduced angiogenesis in chick embryo chorioallantoic membrane (CAM), restrained the trunk angiogenesis in zebrafish, and suppressed angiogenesis and growth of human HCT-15 colorectal cancer xenograft in mice. Western blot assay showed that RA suppressed VEGF-induced phosphorylation of VEGFR2 and its downstream protein kinases including PLCγ1, JAK2, FAK, Src, and Akt. Molecular docking simulation indicated that RA formed hydrogen bonds and hydrophobic interactions within the ATP binding pocket of VEGFR2 kinase domain. Our study firstly provides the evidence that RA has high antiangiogenic potency and explores its molecular basis, demonstrating that RA is a potential agent or lead candidate for antiangiogenic cancer therapy.
authors: Hongqiao International Institute of Medicine, Shanghai Tongren Hospital and Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
authors: Ying-Yun
authors: YY
authors: Guan
authors: Hongqiao International Institute of Medicine, Shanghai Tongren Hospital and Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
authors: Hai-Jun
authors: HJ
authors: Liu
authors: Hongqiao International Institute of Medicine, Shanghai Tongren Hospital and Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
authors: Xin
authors: X
authors: Luan
authors: Hongqiao International Institute of Medicine, Shanghai Tongren Hospital and Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
authors: Jian-Rong
authors: JR
authors: Xu
authors: Hongqiao International Institute of Medicine, Shanghai Tongren Hospital and Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
authors: Qin
authors: Q
authors: Lu
authors: Hongqiao International Institute of Medicine, Shanghai Tongren Hospital and Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
authors: Ya-Rong
authors: YR
authors: Liu
authors: Hongqiao International Institute of Medicine, Shanghai Tongren Hospital and Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
authors: Yun-Ge
authors: YG
authors: Gao
authors: Department of Pharmacy, Shanghai Institute of Health Sciences and Health School Attached to SJTU-SM, 279 Zhouzhu Road, Shanghai 201318, China. Electronic address: zhaomei100@163.com.
authors: Mei
authors: M
authors: Zhao
authors: Hongqiao International Institute of Medicine, Shanghai Tongren Hospital and Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China. Electronic address: hongzhuan_chen@hotmail.com.
authors: Hong-Zhuan
authors: HZ
authors: Chen
authors: Hongqiao International Institute of Medicine, Shanghai Tongren Hospital and Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China. Electronic address: fangchao100@hotmail.com.
authors: Chao
authors: C
authors: Fang
mesh_terms: D031883:Anemone / Q000737:chemistry*; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002642:Chick Embryo; D015179:Colorectal Neoplasms / Q000473:pathology; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D062105:Molecular Docking Simulation; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D015027:Zebrafish / Q000196:embryology
chemical_list: D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D012503:Saponins; C584473:raddeanin A; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Anemone raddeana; Colorectal tumor; Raddeanin A; Tumor angiogenesis; VEGFR2; Zebrafish