Apoptosis Potency Prediction of Steroid Saponin from Gembili (Dioscorea esculenta) as Bcl-2 and Bcl-xL Inhibitors in Colon Cancer

Abstract

Steroid saponins from gembili tuber (Dioscorea esculenta) are natural compounds that are known to have anticancer activity by inducing apoptosis through inhibition of Bcl-2 dan Bcl-xL. This study was determine the potency, mechanism and binding affinity of steroid saponin compounds as Bcl-2 and Bcl-xL inhibitor of colon cancer in silico using molecular docking. In silico assay was carried out using VEGAZZ (use for Bcl-2 protein preparation), Open Babel (use for minimizing the 3D structure of steroid saponin compounds), Autodock Vina in the PyRx 0.8 program (use for molecular docking), and PyMOL, Discovery Studio Visualizer (use for 2D and 3D visualization). The result of molecular docking was a binding affinity value based on the formation of hydrogen and hydrophobic interactions between ligand and receptor, more smaller binding affinity value, more stronger the bond. Data were compared with navitoclax, ABT-737 and obatoclax. The binding affinity between Bcl-2 and navitoclax, ABT-737, obatoclax, prosapogenin A, dioscin, gracillin, diosgenin, protogracillin, dichotomin and protodioscin were –9,8; –8,9; –7,2; –9,0; –8,8; –8,0; –7,9; –8,4; –8,2 and –7,7 kcal/mol. Then the binding affinity between Bcl-xL and navitoclax, ABT-737, obatoclax, prosapogenin A, dioscin, gracillin, diosgenin, protogracillin, dichotomin, and protodioscin were –10,6; –9,3; –8,3; –9,7; –9,4; –8,9; –9,7; –9,1; –9,9 and –8,8 kcal/mol. Based on the results obtained, the steroid saponin compounds of gembili tuber are possible have potential as anti-colon cancer through inhibition of Bcl-2 and Bcl-xL protein in order to increase the regulation of apoptosis. HIGHLIGHTS The main process of apoptosis in the intrinsic pathway is regulated by the Bcl-2 protein family Saponin steroids are triterpenoid modifications commonly found in Dioscoreacease plants including Dioscorea esculenta Steroid saponins compounds of gembili tuber include prosapogenin A, dioscin, gracillin, diosgenin, protogracillin, dichotomin and protodioscin has potential as an anti-colon cancer through inhibition of anti-apoptotic proteins Bcl-2 and Bcl-xL in silico using molecular docking GRAPHICAL ABSTRACT