Adv Pharm Bull. 2019;9(3):462-469.
doi: 10.15171/apb.2019.055
  Abstract View: 27
  PDF Download: 42

Research Article

Synergetic Impact of Combined 5-Fluorouracil and Rutin onApoptosis in PC3 Cancer Cells through the Modulation of P53 GeneExpression

Atefeh Satari 1 ORCiD, Sayed Asadollah Amini 2 ORCiD, Elham Raeisi 3 ORCiD, Yves Lemoigne 4 ORCiD, Esfandiar Heidarian 1 * ORCiD

1 Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
2 Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
3 Department of Medical Physics & Radiology, Shahrekord University of Medical Sciences, Shahrekord, Iran.
4 Institute for Medical Physics, Ambilly, France.

Abstract

Purpose: Prostate cancer is as far the most prevalent male cancer. Rutin (a glycoside fromquercetin flavonoid) displays antioxidant activity leading to cell apoptosis. Combined effects ofrutin with the widely used anti-cancer drug, 5-fluorouracil (5-FU), on prostate cancer cell line(PC3) was investigated herein.Methods: Different concentrations of combined 5-FU and rutin were applied to PC3 cellscompared to separate treatment for 48 hours. Cell viability, as well p53 gene expressionrespectively were assessed by MTT assay and real-time quantitative polymerase chain reaction(qPCR). Changes of Bcl-2 signal protein and apoptosis were determined using western blotand flow cytometry procedures, respectively. Clonogenic assay was used to colony countsassessment.Results: 50% inhibitory concentration (IC50) of separate cell treatment with either rutin and5-FU respectively were 900 μM and 3Mm, while combination index (CI) of combined 5-FU/rutin application reached a level of synergistic effects (0.33). Combination of 5-FU/rutinenhanced apoptosis and p53 gene expression in PC3 cells. PC3 cell colony counts and Bcl-2signaling protein were decreased by 5-FU/rutin combination.Conclusion: Synergistic effects of 5-FU/rutin combination on PC3 cells line enhanced apoptosis,p53 gene expression, and down-regulation of Bcl-2 protein, compared to control separateapplication. 5-FU/rutin combination does seem an interesting therapeutic pathway to be furtherinvestigated.
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Submitted: 26 Nov 2018
Revised: 15 Feb 2019
Accepted: 06 Mar 2019
First published online: 01 Aug 2019
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