The role of rutin and naringin flavonoids in the prevention of drug resistance in colon cancer cells

Cancer, one of the leading causes of death worldwide, continues to be a major health threat. The most common cancers in Turkey in 2020 were lung cancer, breast cancer, colorectal cancer, prostate cancer, and thyroid cancer. These cancers account for more than 50% of all cancers. Colorectal adenocarcinoma usually arises in the epithelial cells of the colon. 5-Fluorouracil (5-FU), a standard chemotherapeutic drug, is actively used in the treatment of colon cancer. However, as chemotherapy progresses, cancer cells develop resistance to 5-FU, and the drug loses its effectiveness. In cases where drug resistance develops, chemotherapy cannot sufficiently inhibit tumor growth, metastasis, and recurrence. Therefore, combination therapies with various chemotherapy agents are often used not only to enhance treatment efficacy but also to reduce the toxicity of these drugs. In combination treatments with compounds found in nature, it is expected to inhibit drug resistance in cells. In addition, as a result of the combined treatment of high doses of genotoxic and cytotoxic chemotherapeutic drugs with compounds, it is aimed to obtain low-dose less side effects and rapid results. Since flavonoids are available in nature and cost-effective, they have been the subject of many cancer researches in recent years. The flavonoids rutin and naringin have been investigated individually for their beneficial effects, including anticancer, antiproliferative, and antioxidative stress. However, the potential effects of combined administration of rutin and naringin with 5-FU on cell death and DNA damage in colon cancer cell lines are unknown. This study investigated the effects of 5-FU combined with rutin and naringin on the colon cancer cell lines HT-29 and Caco-2. This study yielded the first results regarding the synergistic effects of these compounds in the treatment of colon cancer. In the study, rutin, naringin, and 5-FU were applied to colon cancer cells individually and in combination for 24, 48, and 72 hours. Cytotoxicity and genotoxicity analyses were used to determine changes in cell viability following the treatments. Statistical analyses were performed on the obtained data. As a result of the study, it was obtained that both flavonoids had a synergistic effect with 5-FU and could be used as potential chemotherapeutic agents.