Synergistic effects of 5-fluorouracil in combination with diosmetin in colorectal cancer cells

Background:Colorectal cancer (CRC) is among the most common occurring cancer. The management of CRC includes laparoscopic surgery, radiotherapy, chemotherapies and neoadjuvant. However, the conventional chemotherapies have poor impact on combating CRC and are associated with sever toxic effects and high relapse. Therefore, searching for a new combination regimen is a favorable consideration. Objective:The aim of this study was to elucidate the synergistic effect of 5-fluorouracil (5-FU) and diosmetin in an in vitromodel in colorectal cancer cell. Methodology:MTT assay was conducted on HCT-116 cancer cells and treated with concentration gradient of 5-FU and diosmetinindividually and in combination. Combination index (CI) and dose reduction index (DRI) were calculated using Compusyn software.Isobologram analysis and synergism determination was done via Combenefit software tool and synergy score was calculated using SynergyFinder 2.0 software tool. Apoptotic features of cells were determined via AO/PI double staining assay and Annexin V assay using fluorescent microscope and flow cytometry technique, respectively. Results:findings showed that the DRI of 5-FU was 5 folds lower in the combination treatment with an CI value less than one, which indicates the synergistic effect. AO/PI microscopic results revealed signs of apoptosis and dead cells after 72 h of treatment. Flow cytometry analysis confirmed the apoptotic effects of combination was more prominent as compared to 5-FU alone.

Conclusion:The findings of this study offered a potential strategy to reduce the cytotoxicity and enhance the efficacy of 5-FU on colorectal cancer cells through a synergistic study model.