The apoptotic effects of thymoquinone on PC3 cancer cell line: An in vitro and computer-simulated environment study

Introduction & Aim: Anti oxidants such as thymoquinone can induce apoptosis in many tumor cell lines. In this study we evaluate the apoptotic effects of thymoquinone on PC3 cell line. Also, we evaluated the interaction of thymoquinone with BCL-XL, BCL-2 and MCL-1 anti-apoptotic factors by computer-simulated environment.Methods: PC3 cells were treated with different concentrations of thymoquinone and IC50 was evaluated using MTT producer. Apoptotic and cytotoxicity effects of thymoquinone were analyzed using flow cytometry and comet assay, respectively. Changes in energy and the molecular interactions of thymoquinone with BCL-XL, BCL-2 and MCL-1 anti-apoptotic factors were investigated using simulation and molecular docking softwares including Gromacs, Auto Dock and VMD.Results: IC50 value was nearly 40µM. Thymoquinone led to destroy the genome of PC3 and apoptosis. Binding Energy between thymoquinone and BCL-2, BCL-XL and MCL-1 were -4.65, -5.89 and -4.64, respectively. Molecular dynamic (MD) revealed that the RMSD, RMSF, RG and the number of hydrogen and hydrophobic bonds between thymoquinone and residuesof BCL-2, BCL-XL and MCL-1 were significantly (p<0.001) change. Docking and MD analysis demonstrated that BCL-x1 is the most stable in trajectory analysis in all simulations. Thymoquinone make a more stable and stronger connection with BCL-xl compared to BCL-2 and MCL-1 and inhibits BCL-x1 non-competitively.Conclusion: Our results demonstrated that thymoquinone led to apoptosis in PC3 cells this effect is maybe through reducing the Coil, Turn, and Bend structure of BCL-xl and decrease the Rg and RMSD value of BCL-2, BCL-XL, MCL-1.

کلیدواژه ها:

BCL-2 ، BCL-XL ، MCL-1 and molecular dynamic