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

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. 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. 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. 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.