In-Vitro Evaluation of Synergistic Effect of Quercetin on the Anticancer Activities of 5Fluorouracil In MDA.MB231 Breast Cancer Cell Line

Abstract

Breast cancer is the most commonly occurring cancer in women which causes death among women in 140 of 184 countries worldwide and the second most common cancer overall. Breast cancer characterized by the uncontrolled growth of abnormal cells in the mammary gland of the breast or in the ducts that deliver milk to the nipples. Several anticancer drugs are used in the treatment of breast cancer; 5-FU is a chemotherapeutic agent that inhibits thymidylate synthase enzyme, hence interferes with the formation of thymidylate from uracil which lead to inhibition of DNA and RNA synthesis. Quercetin is one of the most powerful flavonoids for protecting the body from reactive oxygen species by increasing the function of antioxidants. It also inhibits both cyclooxygenase and lipoxygenase activities, so decreases the formation of inflammatory metabolites. MTT-based assay revealed that the IC50 of 5-FU and Quercetin were 90.5μM and 4.8 μM respectively after 24 hours against MDA.MB231 breast cancer cell line (Mariotto et al, 2017). Besides, by using Compusyn to calculate the combination index of 5-FU + Quercetin (<0.1) it revealed very strong synergism. According to flow cytometry results, 0.5 fold IC50 combinations showed strong synergism showing the possibility of 5-FU dose reduction while maintaining the cytotoxic effects by combining it with the natural product quercetin. These results were confirmed by flow cytometry for cell cycle analysis where the 0.5 IC50 combinations gave comparable effect to the IC50 5-FU causing cell cycle arrest at G1 phase. In conclusion, the study results showed that addition of Quercetin to 5-FU synergized their individual anticancer effect.