Figure 6. (−)-Gossypol inhibits activation of key proangiogenic molecules involved in VEGF signaling.

A, (−)-gossypol inhibited VEGF-induced activation of Src, FAK, AKT and ERK kinase in endothelial cells. Several key signaling molecules that mediate angiogenesis were analyzed by western blotting assay. HUVECs were starved in serum-free medium for 4~6 h, pretreated with (−)-gossypol for 30 min, and then stimulated with 50 ng/mL VEGF for 5~20 min. Protein was harvested for the analysis. B, schematic model depicted the (−)-gossypol-mediated antiangiogenic signaling pathway. (−)-Gossypol potentially affected the production of VEGF released from tumor cells and endothelial cells by inhibition of Bcl-2 family protein, and further it blocked the activation of VEGFR2 and intracellular kinases in vascular endothelial cells.