By Rachel Walker, Evelyn Buehren

Faculty Mentor: Dr. Laura Sipe

Abstract

5-Fluorouracil Exerts Cytotoxic Chemotherapy Independently of Oxidative Stress Pathways in Breast Cancer Cells

Rachel Walker and Evelyn Buehren

Faculty Advisor: Dr. Laura Sipe

Chemotherapy, the main treatment option for triple-negative breast cancer, targets actively dividing cells resulting in cell death. Many chemotherapies result in the production of reactive oxygen species (ROS). We wanted to examine if oxidative stress is necessary for 5-fluorouracil (5FU) to induce cell death. Specifically, in this study we examined the cell viability of the mouse breast cancer cell lines when treated with 5-FU. After treatment with 5FU for 48 hours, we examined antioxidant gene expression and determined heme oxygenase-1 (HO-1) and methionine sulfoxide reductase B3 (Msrb3) does not change in EO771 cell line. Interestingly, in the 4T1 cell line there was an increase in both HO-1 and MsrB3 with HO-1 being significantly different. To determine if 5FU is effective without oxidative stress we treated both E0771 and 4T1 cells with the known antioxidant, N-acetyl cysteine (NAC) at 1uM. In the E0771 cells, NAC did not impact 5FU cytotoxic effects, indicating that 5FU does not require oxidative stress to kill cancer cells. In the 4T1 cells, no cytotoxic effects of the 5FU were observed even in the absence of NAC. This could suggest that 4T1 cells can maintain oxidative stress levels better than the E0771 cells, causing resistance to 5FU. The next step would be to measure the difference in ROS between these cell lines with the treatment of 5FU and in the absence of NAC. Future work will explore other potential mechanisms of 5FU chemotherapy response. Understanding the mechanism of 5FU across cancer cell lines will better allow us to provide personalized chemotherapy