Lycorine Inhibits Angiogenesis by Docking to PDGFRα

Lyc (Lycorine) is a natural alkaloid derived from medicinal plants of the Amaryllidaceae family. Lyc has been reported to inhibit recurrence and metastasis of different kinds of tumors. However, the Lyc’s effect of angiogenesis and its specific mechanism is still not clear. This study was designed to test the anti-angiogenesis effect of Lyc and explore possible mechanisms. We performed cell experiments to confirm Lyc's inhibitory effect on angiogenesis and employed sunitinib as a positive control. Meanwhile, the synergistic effect of Lyc and sunitinib was also explored. Next, we conducted bioinformatics to predict the potential targets of Lyc and verified them by western blott and immunofluorescence. Molecular docking, kinase activity assays, Biacore assays and cellular thermal shift assays (CETSAs) were applied to elucidate the mechanism by which Lyc inhibited target activity. Lyc inhibited angiogenesis in human umbilical vein endothelial cells (HUVECs). Employing bioinformatics, we found that Lyc's target was PDGFRα and that Lyc attenuated PDGFRα phosphorylation. We also found that Lyc inhibited PDGFRα activation by docking to it to restrain its activity. In addition, Lyc significantly inhibited PDGF-AA-induced angiogenesis. This study provides new insights into the molecular functions of Lyc and indicates its potential as a therapeutic agent for tumor angiogenesis.