INHIBITION OF NADPH OXIDASE ACTIVITY AUGMENTS 5-FLUOROURACIL MEDIATED CELL DEATH IN HUMAN COLON CARCINOMA HCT-116 CELLS

5-Fluorouracil (5-FU) is a well known chemotherapeutic agent, which has been most commonly used for the treatment of colon cancer. 5-FU significantly reduces tumor burden, but the progression of metastasis with the phenotype of drug resistance is a major obstacle in successful anti-cancer therapy. The cellular redox balancing genes and proteins participates in cancer metastasis and drug resistance. The cellular redox balance is linked with the level of intracellular ROS and its source, NADPH Oxidase (NOX). Compelling evidences suggest that the activation of various NOX isoforms modulates the development and progression of malignancies. However, the role of NOX enzyme activation during 5-FU treatment has not been investigated. In the present study, we aimed to analyze the role of NOX activity upon 5-FU treatment on HCT-116 cells. We found that the 5-FU inhibits cell proliferation and induces cell death in HCT-116 cells. Moreover elevated NOX activity and subsequent ROS generation was found in 5-FU treated HCT-116 cells. Interestingly, the inhibition of NOX activity using known inhibitor Diphenylene iodonium (DPI) augmented 5-FU mediated cell death. These findings suggest that NOX activation resists 5-FU mediated cell death in HCT-116 cells. Therefore, targeting NOX enzymes may be a potent therapeutic strategy to increase the efficacy of 5-FU treatment in cancer therapy.