Adv Pharm Bull. 2019;9(3):490-496.
doi: 10.15171/apb.2019.058
  Abstract View: 23
  PDF Download: 28

Research Article

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

Javad Saffari_Chaleshtori 1 ORCiD, Ehsan Heidari-Sureshjani 2, Fahimeh Moradi 3, Esfandiar Heidarian 4 * ORCiD

1 Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran.
2 Young Researchers and Elites Club, Islamic Azad University, Shahrekord Branch, Shahrekord, Iran.
3 Cellular & Molecular, Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
4 Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Abstract

Purpose: Since active plant ingredients can induce apoptosis in many tumors, in this studywe evaluate the apoptotic effects of thymoquinone (TQ) on PC3 cells. Also, we predicted theinteraction of TQ with BCL-XL, BCL-2, and MCL-1anti-apoptotic factors by computer-simulatedenvironment.Methods: PC3 cells were treated with different concentrations of TQ (0- 80 μM) and IC50 wasdetermined 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 andMCL-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 inducingapoptosis. 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 andhydrophobic 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 comparedto 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 toreduction in the Coil, Turn, and Bend structure of BCL-XL but also caused a decrease in the Rgand RMSD value of BCL-XL, MCL-1, and BCL-2.
First name
 
Last name
 
Email address
 
Comments
 
Security code


Article Viewed: 23

Your browser does not support the canvas element.


PDF Downloaded: 28

Your browser does not support the canvas element.

Submitted: 10 Feb 2019
Revised: 18 Mar 2019
Accepted: 14 Apr 2019
First published online: 01 Aug 2019
EndNote EndNote

(Enw Format - Win & Mac)

BibTeX BibTeX

(Bib Format - Win & Mac)

Bookends Bookends

(Ris Format - Mac only)

EasyBib EasyBib

(Ris Format - Win & Mac)

Medlars Medlars

(Txt Format - Win & Mac)

Mendeley Web Mendeley Web
Mendeley Mendeley

(Ris Format - Win & Mac)

Papers Papers

(Ris Format - Win & Mac)

ProCite ProCite

(Ris Format - Win & Mac)

Reference Manager Reference Manager

(Ris Format - Win only)

Refworks Refworks

(Refworks Format - Win & Mac)

Zotero Zotero

(Ris Format - FireFox Plugin)