RESUMEN
Angiogenesis is a strictly controlled process defined as the formation of new blood vessels essential for certain physiologic and pathologic conditions where the latter includes tumor growth, development, and metastasis. Thus, inhibiting angiogenesis along with other anticancer strategies such as chemotherapy seems to be invaluable for reaching an optimal outcome in cancer patients. It has been shown that some natural plant-derived compounds are capable of preventing the formation of these new blood vessels in the tumor and also inhibit the proliferation and growth of the cancer cells. In this review, we intend to introduce plants with anti-angiogenic properties and discuss their related features.
RESUMEN
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 αVß3 integrin and VEGFR1. Electrophoresis analysis of the purified protein revealed a single band with a molecular mass of about 3kDa. Treatment with TICMS at six doses resulted in a significant decrease of endothelial cell proliferation with an IC50 value of about 20µg/ml. Tubulogenesis assay revealed that a dose dependent anti-angiogenic activity of TICMS (5-40µg/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 αVß3 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.