Synergistic Effect of 5-Fluorouracil Combined with Naringin in MDA-MB-231 Human Breast Cancer Cells

Abstract

Antimetabolite established as a successful therapeutics for advanced-stage breast cancers, but has recurrently shown to exhibit major side effects, which restrict drug therapy interventions. The most widely used chemotherapeutic agent is 5-Fluorouracil, however the recent report suggests that its antineoplastic activity is limited due to drug resistance developed by the cancer cells. The resistance results in the decrease in efficacy of 5-FU to improve either invasive disease-free survival or overall survival. In order to enhance 5-Fluorouracil mediated cytotoxicity, we have attempted the combination of the natural compound Naringin with 5-Fluorouracil. The combination of 5-Fluorouracil and Naringin inhibited the proliferation of MDA-MB-231 breast cancer cells determined using MTT assay. Importantly, combined treatment showed synergistic enhancement of breast cancer cell cytotoxicity. We next confirmed the cytotoxicity profile of the combination 5-Fluorouracil and Naringin in MDA-MB-231 breast cancer cells with trypan blue-based cell viability assay and determined that the IC50 value is 80 μM. When 5-Fluorouuracil and Naringin incubated there is a 7–10-fold increase in cytotoxic effect on breast cancer cells. These results demonstrates that application of naringin as an adjuvant treatment during 5-Fluorouracil administration might enhance the chemotherapeutic efficacy of 5-Fluorouracil.