Anti-angiogenic potential of trypsin inhibitor purified from Cucumis melo seeds: Homology modeling and molecular docking perspective

Abstract Melons have a good source of protease inhibitors. Its fruit and seeds have been used as a traditional medicine. However, its effects on angiogenesis and mechanism of its action remain elusive. Herein trypsin inhibitor from aqueous extract of C. melo seeds (TICMS) was purified. Its effects on different steps of angiogenesis were evaluated. Also, we examined its effects on migration and angiogenesis of endothelial cells. Three dimensional model of TICMS protein was accurately built in which TICMS docked to α V β 3 integrin and VEGFR1. Electrophoresis analysis of the purified protein revealed a single band with a molecular mass of about 3 kDa. Treatment with TICMS at six doses resulted in a significant decrease of endothelial cell proliferation with an IC 50 value of about 20 μg/ml. Tubulogenesis assay revealed that a dose dependent anti-angiogenic activity of TICMS (5–40 μg/ml). Also, TICMS had inhibitory effects on VEGF, MMP-2 and MMP-9 secretion. Our docking result speculated that TICMS could bind to the cleft between the α V β 3 integrin and it able to decrease the activity of this receptor. The TICMS was also able to interact with VEGFR1 receptor, but with low probability. Based on our study, TICMS could be used as a specific angiogenesis inhibitor.