Abstract
PurposeAngiogenesis, or new blood vessel formation from existing one, plays both beneficial and detrimental roles in living organisms in different aspects. Vascular endothelial growth factor (VEGF), a signal protein, well established as key regulator of vasculogenesis and angiogenesis. VEGF ensures oxygen supply to the tissues when blood supply is not adequate, or tissue environment is in hypoxic condition. Limited expression of VEGF is necessary, but if it is over expressed, then it can lead to serious disease like cancer. Cancers that have ability to express VEGF are more efficient to grow and metastasize because solid cancers cannot grow larger than a limited size without adequate blood and oxygen supply. Anti-VEGF drugs are already available in the market to control angiogenesis, but they are often associated with severe side-effects like fetal bleeding and proteinuria in the large number of patients. To avoid such side-effects, new insight is required to find potential compounds as anti-VEGF from natural sources. In the present investigation, molecular docking studies were carried out to find the potentiality of Withaferin A, a key metabolite of Withania somnifera, as an inhibitor of VEGF.MethodsMolecular Docking studies were performed in DockingServer and SwissDock. Bevacizumab, a commercial anti-VEGF drug, was used as reference to compare the activity of Withaferin A. X-ray crystallographic structure of VEGF, was retrieved from Protein Data Bank (PDB), and used as drug target protein. Structure of Withaferin A and Bevacizumab was obtained from PubChem and ZINC databases. Molecular visualization was performed using UCSF Chimera.ResultsWithaferin A showed favorable binding with VEGF with low binding energy in comparison to Bevacizumab. Molecular Docking studies also revealed potential protein-ligand interactions for both Withaferin A and Bevacizumab.ConclusionsConclusively our results strongly suggest that Withaferin A is a potent anti-VEGF agent as ascertained by its potential interaction with VEGF. This scientific hypothesis might provide a better insight to control angiogenesis as well as to control solid cancer growth and metastasis.Electronic supplementary materialThe online version of this article (doi:10.1186/2193-9616-1-11) contains supplementary material, which is available to authorized users.
Highlights
Angiogenesis is a complex process, where angiogenic endothelial cells undergo a complex process that includes the secretion of metallo-proteases, cell migration, endothelial cell division, and proliferation, including the new blood vessel formation from the endothelium of a pre-existing vasculature (Bruick and McKnight 2001; Cébe-Suarez et al 2006)
Conclusively our results strongly suggest that Withaferin A is a potent anti-Vascular endothelial growth factor (VEGF) agent as ascertained by its potential interaction with VEGF
Vascular endothelial growth factor (VEGF) is considered as one of the most vital pro-angiogenic factors involved in tumor angiogenesis (Ferrara 2001; Drevs et al 2004; Ferrara et al 2003)
Summary
Angiogenesis is a complex process, where angiogenic endothelial cells undergo a complex process that includes the secretion of metallo-proteases, cell migration, endothelial cell division, and proliferation, including the new blood vessel formation from the endothelium of a pre-existing vasculature (Bruick and McKnight 2001; Cébe-Suarez et al 2006). Angiogenesis is involved in pathogenesis of various disorders like age-related macular degeneration, proliferative retinopathies, psoriasis, rheumatoid arthritis, and most the common fatal disorder, solid cancer (Ruggeri et al 2003; Folkman 1995; Ferrara 2001; Garner 1994). Angiogenesis can be controlled through different anti-angiogenic and proangiogenic factors (Drevs et al 2004; Petrova et al 1999). Controlling angiogenesis, we can ensure limited growth of solid cancer, because cancer cell will starve without extra supply of nutrients and oxygen (Folkman 1995; Ferrara 2002, 2004). Vascular endothelial growth factor (VEGF) is considered as one of the most vital pro-angiogenic factors involved in tumor angiogenesis (Ferrara 2001; Drevs et al 2004; Ferrara et al 2003). VEGF family comprising of glycoproteins designated as VEGF-A, VEGF-B,VEGF-C, VEGF-D, VEGF-E, placental growth factor (PGF), and VEGF-F are involved in the regulation of angiogenesis (Ball et al 2007; Lee et al 2010; Otrock et al 2007; Fayette and Soria 2005)
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