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Abstract Title:

Anti-angiogenic and anti-tumor activity of Bavachinin by targeting hypoxia-inducible factor-1α.

Abstract Source:

Eur J Pharmacol. 2012 Sep 15 ;691(1-3):28-37. Epub 2012 Jul 1. PMID: 22760073

Abstract Author(s):

Manoj Nepal, Hwa Jung Choi, Bo-Yun Choi, Se Lim Kim, Jae-Ha Ryu, Do Hee Kim, Young-Hoon Lee, Yunjo Soh

Article Affiliation:

Manoj Nepal

Abstract:

Hypoxia-inducible factor-1 (HIF-1) consists of two subunits, the HIF-1β, which is constitutively expressed, and HIF-1α, which is oxygen-responsive. HIF-1α is over-expressed in response to hypoxia, increasing transcriptional activity linked to tumor progression, angiogenesis, metastasis, and invasion. This study aimed to demonstrate that the natural compound, Bavachinin, has potent anti-angiogenic activity in vitro and in vivo. Bavachinin inhibited increases in HIF-1α activity in human KB carcinoma (HeLa cell derivative) and human HOS osteosarcoma cells under hypoxia in a concentration-dependent manner, probably by enhancing the interaction between von Hippel-Lindau (VHL) and HIF-1α. Furthermore, Bavachinin decreased transcription of genes associated with angiogenesis and energy metabolism that are regulated by HIF-1, such as vascular endothelial growth factors (VEGF), Glut 1 and Hexokinase 2. Bavachinin also inhibited tube formation in human umbilicalvein endothelial cells (HUVECs) as well as in vitro migration of KB cells. In vivo studies showed that injecting Bavachinin thrice weekly for four weeks significantly reduced tumor volume and CD31 expression in nude mice with KB xenografts. These data indicate that Bavachinin could be used as a therapeutic agent for inhibiting tumor angiogenesis.

Study Type : Animal Study, In Vitro Study

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