Anticancer Property Of Green Material Through Computational Approach
Nupur Jauhari, Gajula MNV Prasad, Neelam Sharma, Navneeta Bharadvaja
Volume 2, Issue 6, Page 378-383, Year 2017 | DOI: 10.5185/amp.2017/606
Keywords: Colon cancer, molecular docking, stigmasterol, TACE, TNF-α
Abstract: The purpose of research: Colorectal cancer is third most prevalent cancer in developed countries with increasing cases in developing countries. Studies show that the chronic intestinal inflammation is associated with increased risk of developing colorectal cancer. Inflammation is an immunological response to external damaging stimuli and is govern by an endogenous pyrogen and pleiotropic pro-inflammatory cytokine, tumor necrosis factor-alpha (TNF-α). TNF-α plays an important role in the development of humoral immune response. Production of TNF-α has been implicated in various other pathologies including diabetes, osteoporosis, multiple sclerosis and inflammatory bowel diseases also. Several studies have shown that anti-inflammatory effect of stigmasterol, a phytosterol of an endangered medicinal plant Chlorophytum borivilianum, is mediated by suppression of TNF-α. The latter is synthesized as a membrane-anchored precursor. The soluble form of TNF-α is released into extracellular space by tumor necrosis factor alpha converting enzyme (TACE), a multidomain metalloproteinase.
Principal results: We have investigated the anti-cancer effect of the green material against colon cancer by using computational molecular docking and molecular dynamics simulations approach. With this study, we tried to explore stigmasterol as a potential inhibitor of TACE. The active cleft of TACE has a catalytic zinc residue at its centerpentacoordinate by the three-imidazole N2 atoms of His 405, His 409, His 415. Along with these residues Glu 406, Met 345, Pro 437, Trp 312, Asp 344 around the zinc atom constitute the active site. The docked complex formed a hydrogen bond with Gly 346 and showing hydrophobic interactions with other active site residues. Molecular dynamics simulations confirmed that hydrogen-bond connectivity has not been lost throughout our simulations of 30ns. Computed RSMD suggests that docked complex is stable.
Major conclusions: Therapeutic blockade of TACE could be highly beneficial in case of chronic inflammatory conditions including colon cancer. In the present study, we conclude that stigmasterol, a green material may be considered as a possible therapeutic agent in the treatment of colon cancer and the same can certainly be confirmed through in vivo studies and clinical trials to confirm their effectiveness in patients. Copyright © 2017 VBRI Press.