The Role of SIRT5 and p53 Proteins in the Sensitivity of Colon Cancer Cells to Chemotherapeutic Agent 5-Fluorouracil

In the treatment of colorectal cancer, it is important to develop drug combinations that will increase the effectiveness of chemotherapy and to determine the molecular targets of the drugs. Therefore, combined therapies that can increase the sensitivity of 5-Fluorouracil (5-FU) and the molecular pathways involved in this process are important in the treatment of the disease. Here we examined the SIRT5 (Resveratrol and Suramin) and p53 (Nutlin3a) modulators alone or in combination with 5-FU on the proliferation of colon cancer cells and effect of 5-FU on the SIRT5 and FOXO3a protein expressions whether p53 dependent or independent manner. According to our MTT assay results, Resveratrol (RSV), Nutlin3a and Suramin was found to be more effective in HCT-116 p53+/+ cells and these differences were evaluated together with the effect of 5-FU on the SIRT5, FOXO3a and Bim protein expressions in HCT-116 p53 +/+ and HCT-116 p53 −/− cells. SIRT5 is known to deacetylate FOXO3a which plays roles in the induction of apoptosis via Bim protein. Our western blot experiment results showed that while Suramin decreased SIRT5 and RSV decreased FOXO3a protein expressions significantly in HCT-116 p53 −/− cells, 5-FU decreased significantly SIRT5 and FOXO3a protein expressions in a p53 independent manner. In this study, the effect of 5-FU on SIRT5 and FOXO 3a proteins was determined for the first time in HCT-116 p53 +/+ and HCT-116 p53 −/− cells. These results may help the discovery of new markers in colon cancer treatment.