The Cytotoxic Effect of 2-Deoxy-D-Glucose Combination with 5-Fluorourasil and NO-Aspirin on Mammary Adenocacinoma Cell Line

Abstract

2-deoxy-D-glucose (2DG) and NO-Aspirin (NO-ASA) are new anticancer agents that are under intense clinical investigation for their remarkable cytotoxic activity. Combining 2DG, which targets glucose metabolism, with other agents mainly the DNA- and the mitochondrial-damaging agents represent a promising chemotherapeutic strategy.  In this study, we investigated the cytotoxic effects of 2DG, 5-fluorourasil (5FU), and NO-ASA on AMN3 breast cancer model, in addition to the cytotoxic effects of 2DG combination with 5FU and NO-ASA on the same cells. The cytotoxic activity of 2DG, 5FU, and NO-ASA was measured by using the MTT assay at 24, 48, and 72 hr. Then 2DG was combined with 5FU and NO-ASA in a constant concentration ratio based on their corresponding IC50s and the inhibition of cell growth was measured by MTT assay at 72hr. Median effect analysis was conducted to determine the cytotoxic activity of the combinations. 2DG, 5FU, and NO-ASA were found to exert a significant dose- and time-dependant growth inhibition on AMN3 cells. The mean combination index values reveal an additive effect for both combinations. This study demonstrated that 2DG and NO-ASA are capable of inhibiting the breast tumor growth effectively. It also shows that 2DG/5FU and 2DG/NO-ASA combinations result in mean additive effects with good dose reduction index values that have the advantages of reducing the toxicity, adverse effects, and the drug resistance in cancer patients.

Key words: 2-deoxy-D-glucose (2DG), NO-Aspirin (NO-ASA), 5-fluorourasil (5FU), Glucose metabolism, Median effect analysis, Breast cancer