The Effects of Thymoquinone on Viability, and Antiapoptotic Factors (BCLXL, BCL2, MCL1) in Prostate Cancer (PC3) Cells: An In Vitro and ComputerSimulated Environment Study

Purpose: Since active plant ingredients can induce apoptosis in many tumors, in this study we evaluate the apoptotic effects of thymoquinone (TQ) on PC3 cells. Also, we predicted the interaction of TQ with BCLXL, BCL2, and MCL1antiapoptotic factors by computersimulated environment. Methods: PC3 cells were treated with different concentrations of TQ (0 80 µM) and IC50 was determined using 3(4, 5dimethylthiaztol2yl)2, 5diphenyltetrazolium bromide (MTT) assay. Apoptotic and cytotoxicity effects of TQ were analyzed using flowcytometry and comet assay, respectively. Changes in energy and the molecular interactions of TQ with BCLXL, BCL2 and MCL1 antiapoptotic factors were investigated using simulation. Results: IC50 value was 40 µM. TQ led to the destruction of the genome of PC3 cells and inducing apoptosis. Molecular dynamics (MD) revealed that the root meansquare deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), and the number of hydrogen and hydrophobic bonds between TQ and residues of BCL2, BCLXL and MCL1were significantly (P lt;0.001) changed. TQ makes a more stable and stronger connection with BCLXL compared to BCL2 and MCL1 and inhibits BCLXL noncompetitively. Conclusion: Our results demonstrated that TQ not only led to apoptosis, at least partly, due to reduction in the Coil, Turn, and Bend structure of BCLXL but also caused a decrease in the Rg and RMSD value of BCLXL, MCL1, and BCL2.