title: Xanthatin, a novel potent inhibitor of VEGFR2 signaling, inhibits angiogenesis and tumor growth in breast cancer cells.
abstract: Anti-angiogenesis targeting vascular endothelial growth factor receptor 2 (VEGFR2) has emerged as an important tool for cancer treatment. In this study, we described a novel VEGFR2 inhibitor, xanthatin, which inhibits tumor angiogenesis and growth. The biochemical profiles of xanthatin were investigated using kinase assay, migration assay, tube formation, Matrigel plug assay, western blot, immunofluorescence and human tumor xenograft model. Xanthatin significantly inhibited growth, migration and tube formation of human umbilical vascular endothelial cell as well as inhibited vascular endothelial growth factor (VEGF)-stimulated angiogenesis. In addition, it inhibited VEGF-induced phosphorylation of VEGFR2 and its downstream signaling regulator. Moreover, xanthatin directly inhibit proliferation of breast cancer cells MDA-MB-231. Oral administration of xanthatin could markedly inhibit human tumor xenograft growth and decreased microvessel densities (MVD) in tumor sections. Taken together, these preclinical evaluations suggest that xanthatin inhibits angiogenesis and may be a promising anticancer drug candidate.
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province Clinical Ophthalmology Institute Nanchang 330006, China ; Department of Endocrinology and Metabolism, The Third Hospital of Nanchang Nanchang 330009, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Acupuncture and Moxibustion, Hangzhou TCM Hospital of Zhejiang Chinese Medical University Hangzhou 310007, Zhejiang Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province Clinical Ophthalmology Institute Nanchang 330006, China.
authors.forename: Chong Gang
authors.initials: CG
authors.lastname: Pei
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province Clinical Ophthalmology Institute Nanchang 330006, China.
authors.forename: Yun Yan
authors.initials: YY
authors.lastname: Li
authors.affiliation: Department of Endocrinology and Metabolism, The Third Hospital of Nanchang Nanchang 330009, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Tu
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province Clinical Ophthalmology Institute Nanchang 330006, China.
authors.forename: Gui Ping
authors.initials: GP
authors.lastname: Gao
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province Clinical Ophthalmology Institute Nanchang 330006, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shao
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D005663:Furans / Q000494:pharmacology*; D006801:Humans; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D005663:Furans; C022186:xanthatin; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: VEGFR2; Xanthatin; angiogenesis; breast cancer