The Effects of Thymoquinone on Viability, and Anti-apoptotic Factors (BCL-XL, BCL-2, MCL-1) in Prostate Cancer (PC3) Cells: An In Vitro and Computer-Simulated Environment Study

Abstract

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 BCL-XL, BCL-2, and MCL-1anti-apoptotic factors by computer-simulated environment. Methods: PC3 cells were treated with different concentrations of TQ (0- 80 µM) and IC50 was determined using 3-(4, 5-dimethylthiaztol-2-yl)-2, 5-diphenyltetrazolium 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 BCL-XL, BCL-2 and MCL-1 anti-apoptotic 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 mean-square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), and the number of hydrogen and hydrophobic bonds between TQ and residues of BCL-2, BCL-XL and MCL-1were significantly (P<0.001) changed. TQ makes a more stable and stronger connection with BCL-XL compared to BCL-2 and MCL-1 and inhibits BCL-XL non-competitively. 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 BCL-XL but also caused a decrease in the Rg and RMSD value of BCL-XL, MCL-1, and BCL-2.

Thymoquinone Potentially Modulates the Expression of Key Onco- and Tumor Suppressor miRNAs in Prostate and Colon Cancer Cell Lines: Insights from PC3 and HCT-15 Cells

“…Notably, a significant reduction in cell viability was observed in the concentration range of 50 to 210 μM for HCT-15, which is consistent with the findings in the HCT-116 cell line reported by Özkoç [ 64 ], who observed a marked decrease in cell viability in the range of 60 to 200 µM, and the IC 50 value for TQ was determined to be 68 µM at 24 h [ 64 ]. Additionally, Saffari-Chaleshtori [ 60 ] showed a notable decrease in cell viability in a range of 20 to 70 μM for PC3 cell lines, reporting an IC 50 of 40 μM, which is consistent with our assay obtaining an IC 50 of 55.83 μM. This similarity in the concentration range and the IC 50 values supports the notion that TQ exerts a comparable inhibitory effect on the proliferation of colon and prostate cancer cell lines.…”

“…The focus on utilizing plant extracts, such as TQ derived from Nigella sativa , as a potential source of anticancer compounds offers promising prospects [ 23 ]. Several research studies have demonstrated that TQ possesses the ability to suppress cell proliferation and enhance apoptosis in malignant cells [ 60 , 61 , 62 , 63 ]. Prior research has demonstrated that TQ can induce dose-dependent cell death in colon and prostate cancer cell models, including the HCT-116 human colorectal carcinoma cell line, the HT-29 human colorectal adenocarcinoma cell line, and the PC3 prostatic adenocarcinoma cell line [ 60 , 64 , 65 ].…”

Cytotoxic Activity, and Molecular Docking of Indole Alkaloid Voacangine and Bisindole Alkaloid Vobtusine, Vobtusine Lactone from the Indonesian Plant: Voacanga foetida (Blume) Rolfe

“…The voacangine has a simpler structure, this is what makes it easier for voacangine to enter the binding site of the Bcl-2 receptor. This statement is supported by (Saffari-Chaleshtori et al, 2019) who reported the inhibitory activity of thymoquinone against Bcl-2. Even though when interacting with the Bcl-2 receptor, this compound does not form hydrogen bonds at all, this compound has a simple spatial structure that allows easy entry to the Bcl-2 receptor binding site.…”

Fibronectin Modulates the Expression of miRNAs in Prostate Cancer Cell Lines

“…In castration-resistant and androgen-independent Pca, as in the case of PC-3 cells, MCL-1 is upregulated, resulting in resistance to apoptosis and a worse prognosis (65). Other authors have showed increased apoptosis in PC-3 cells after treatment with thymoquinone, an agent capable of negatively regulating MCL-1 (66). Other studies also demonstrate higher cell death rates in PC-3 cells after treatment with drugs that inhibit MCL-1 (67,68).…”