Lycorine inhibits angiogenesis by docking to PDGFRα

Area of Science:

• Pharmacology
• Molecular Biology
• Biochemistry

Background:

• Lycorine (Lyc) is a natural alkaloid from the Amaryllidaceae family with reported anti-tumor properties.
• The specific mechanisms by which Lyc affects angiogenesis remain unclear.
• Understanding Lyc's anti-angiogenic effects is crucial for developing new cancer therapies.

Purpose of the Study:

• To investigate the anti-angiogenic effect of Lycorine (Lyc).
• To elucidate the molecular mechanisms underlying Lyc's action on angiogenesis.
• To explore the potential synergistic effect of Lyc with sunitinib.

Main Methods:

• Cell-based assays using human umbilical vein endothelial cells (HUVECs).
• Bioinformatic analysis to predict Lyc targets.
• Western blotting, immunofluorescence, molecular docking, kinase activity assays, Biacore, and CETSA to verify targets and mechanisms.
• Inhibition assays using PDGF-AA.

Main Results:

• Lycorine (Lyc) demonstrated significant inhibition of angiogenesis in HUVECs.
• Bioinformatics identified PDGFRα as a key target of Lyc.
• Lyc attenuated PDGFRα phosphorylation and inhibited its activation through direct binding.
• Lyc effectively suppressed PDGF-AA-induced angiogenesis.

Conclusions:

• Lycorine (Lyc) possesses potent anti-angiogenic properties.
• Lyc targets and inhibits PDGFRα signaling, a critical pathway in angiogenesis.
• Lyc shows potential as a therapeutic agent for treating tumor angiogenesis.