title: Rhamnazin, a novel inhibitor of VEGFR2 signaling with potent antiangiogenic activity and antitumor efficacy.
abstract: Anti-angiogenesis targeting vascular endothelial growth factor receptor 2 (VEGFR2) has emerged as an important tool for cancer therapy. The identification of new drugs from natural products has a long and successful history. In this study, we described a novel VEGFR2 inhibitor, rhamnazin, which inhibits tumor angiogenesis and growth. Rhamnazin significantly inhibited proliferation, migration and tube formation of human umbilical vascular endothelial cells (HUVECs) in vitro as well as inhibited sprouts formation of rat aorta ring. In addition, it inhibited vascular endothelial growth factor (VEGF)-induced phosphorylation of VEGFR2 and its downstream signaling regulator in HUVECs. Moreover, rhamnazin could directly inhibit proliferation of breast cancer cells MDA-MB-231 in vitro and in vivo. Oral administration of rhamnazin at a dose of 200 mg/kg/day could markedly inhibited human tumor xenograft growth and decreased microvessel densities (MVD) in tumor sections. Taken together, these preclinical evaluations suggest that rhamnazin 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, No.17 Yongwaizheng Street, Donghu District, Nanchang 330006, Jiangxi Province, China; Department of Endocrinology and Metabolism, The Third Hospital of Nanchang, Nanchang Key Laboratory of Diabetes, No.1 Qianjing Road, Xihu District, Nanchang 330009, Jiangxi Province, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Medical Genetics, College of Basic Medical Science of Nanchang University, No.461 Bayi Road, Donghu District, Nanchang 330006, Jiangxi Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cai
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province Clinical Ophthalmology Institute, No.17 Yongwaizheng Street, Donghu District, Nanchang 330006, Jiangxi Province, China. Electronic address: profchonggangpei@163.com.
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, No.17 Yongwaizheng Street, Donghu District, Nanchang 330006, Jiangxi Province, China. Electronic address: profyishao@163.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shao
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D044948:Flavonols / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D029595:Orchidaceae / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D044948:Flavonols; C000597862:rhamnazin; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Angiogenesis; Breast cancer; Rhamnazin; VEGFR2