Investigation of in-vitro biological behavior and pro-angiogenic potential of baicalein as hypoxia-mimicking agent

Abstract

In bone tissue engineering, vascularization is important for cell survival and a successful surgical procedure. Vascularization can be enhanced by hypoxia, but it is not possible to create hypoxia in the body. The present study describes functional biological potential of baicalein, a chemical hypoxia-mimicking agent and hypoxia-enhanced in vitro pro-angiogenesis of human osteosarcoma cell line. Relationship between expression of hypoxia-inducing factor-1a (HIF1α) and pro-angiogenesis in oteosarcoma cell line without affecting osteogenic potential were studied. The HIF-1α pathway along with VEGF expression were used to test for pro- angiogenic effects, while ALP expression was used to measure any changes in osteoinductive potential. Baicalein (C₁₅H₁₀O₅) showed increased HIF-1α stabilization and nuclear translocation, hypoxia responsive element activation and VEGF expression, all of which point to a marked proangiogenic effect. ALP expression reduced significantly in response to baicalein when compared to osteogenic medium. These studies demonstrated that baicalein (C₁₅H₁₀O₅) has a high potential as a viable hypoxia mimicking agent.

Keywords: Hypoxia, angiogenesis, osteosarcoma, VEGF, HIF-1α, baicalein