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-Fluourouracil (5-FU), a chemotherapeutic agent used in the treatment of colon cancer, and also 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 expressions whether p53 dependent or independent manner. p53 protein expression is activated by nutlin3a in HCT-116 p53 +/+ cells and HCT-116 p53 -/-cells were used as counterpart cells that did not express p53. According to our MTT assay results, we showed that these modulators have signi cant effects on the sensitivity of both cells to 5-FU. In p53+/+ cells, Resveratrol (RSV) and Nutlin3a and in p53 -/-cells, Suramin was found to be more effective. These differences were evaluated together with the effect of 5-FU on the SIRT5-FOXO3a-Bim axis in p53 +/+ and p53 -/-cells. SIRT5 is known to deactivate FOXO3a which plays a role in the induction of apoptosis via Bim. Our western blot experiment results showed that while Suramin decreased SIRT5 and RSV decreased FOXO3a protein expressions signi cantly in HCT-116 p53 -/-cells, 5-FU decreased signi cantly SIRT5 and FOXO3a protein expressions p53 independently. These results may help the discovery of new markers in colon cancer treatment.

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-Fluourouracil (5-FU), a chemotherapeutic agent used in the treatment of colon cancer, and also 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 expressions whether p53 dependent or independent manner. p53 protein expression is activated by nutlin3a in HCT-116 p53 +/+ cells and HCT-116 p53 -/- cells were used as counterpart cells that did not express p53. According to our MTT assay results, we showed that these modulators have significant effects on the sensitivity of both cells to 5-FU. In p53+/+ cells, Resveratrol (RSV) and Nutlin3a and in p53 -/- cells, Suramin was found to be more effective. These differences were evaluated together with the effect of 5-FU on the SIRT5-FOXO3a-Bim axis in p53 +/+ and p53 -/- cells. SIRT5 is known to deactivate FOXO3a which plays a role in the induction of apoptosis via Bim. 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 p53 independently. These results may help the discovery of new markers in colon cancer treatment.