title: Antiangiogenic effect of licochalcone A.
abstract: To date, no antiangiogenic activity has been demonstrated for licochalcone A (LicA), a major phenolic constituent of Glycyrrhiza inflata, although it shows significant antitumor activity in human malignant cell lines. Our previous work demonstrated that LicA down-regulates inflammatory responses to lipopolysaccharide in murine macrophages. The purpose of the present study was to evaluate whether LicA inhibits angiogenesis, which is crucial for cancer development and progression. LicA significantly inhibited proliferation (20 microM), migration (5-20 microM), and tube formation (10-20 microM) of human umbilical vascular endothelial cells (HUVECs) as well as microvessel growth from rat aortic rings (10-20 microM). Furthermore, LicA significantly inhibited the growth of CT-26 colon cancer implants in BALB/c mice, with fewer CD31- and Ki-67-positive cells but more apoptotic cells. The underlying antiangiogenic mechanism of LicA correlated with down-regulation of vascular endothelial growth factor receptor (VEGFR)-2 activation. Our findings provide the first evidence that LicA inhibits angiogenesis in vitro and in vivo, perhaps by blocking VEGF/VEGFR-2 signaling. Inhibition of tumor growth may be attributed, at least in part, to decreased angiogenesis in LicA-treated mice. These findings emphasize the potential use of LicA against tumor development and progression in which angiogenesis is stimulated.
authors.affiliation: Center for Efficacy Assessment and Development of Functional Foods and Drugs, Hallym University, Chuncheon 200-702, Republic of Korea.
authors.forename: Yoon Hee
authors.initials: YH
authors.lastname: Kim
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Shin
authors.forename: Dae Hwan
authors.initials: DH
authors.lastname: Kim
authors.forename: Hee Hwan
authors.initials: HH
authors.lastname: Lee
authors.forename: Jung Han Yoon
authors.initials: JH
authors.lastname: Park
authors.forename: Jin-Kyung
authors.initials: JK
authors.lastname: Kim
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects; D047188:Chalcones / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000098:blood supply / Q000188:drug therapy; D042783:Endothelial Cells / Q000187:drug effects; D006035:Glycyrrhiza / Q000737:chemistry; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D034622:RNA Interference; D051381:Rats; D015398:Signal Transduction; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors
chemical_list: D047188:Chalcones; D040301:Vascular Endothelial Growth Factor Receptor-2; C070840:licochalcone A