Wogonin Inhibits Angiogenesis Via a c-Myc/Hif-1α–dependent Pathway in Multiple Myeloma

Wogonin, a plant-derived flavone, has been shown to inhibit tumor angiogenesis. Angiogenesis is associated with multiple myeloma (MM) progression. However, the mechanisms that Wogonin inhibits angiogenesis in MM microenvironment are not well known. In this study, we investigated Wogonin inhibited tumor angiogenesis that correlated with the inhibition the secretion of vascular endothelial growth factor (VEGF) in MM cells. The c-Myc/Hif-1α–dependent pathway was essential to regulate MM cell-mediated angiogenesis and contributed to tumor growth. Wogonin inhibited c-Myc activation and down-regulated the expression of c-Myc and Hif-1α. Functionally, based on transient knockdowns and overexpression, our data delineate Wogonin inhibited VEGF production and secretion mediating tumor angiogenesis via c-Myc/Hif-1α–dependent pathway. Our data, therefore, identify Wogonin as a novel anti-angiogenesis compound to inhibit tumor promotion in MM.