Date of Award

Winter 12-15-2024

Document Type

Honors Project

Degree Name

Bachelor of Science

Department

Biological Sciences

Department Chair or Program Director

Dr. Dianne Baker

First Advisor

Dr. Laura Sipe

Second Advisor

Dr. Ginny Morris

Third Advisor

Dr. Randell Reif

Major or Concentration

Biology

Abstract

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with treatment limited to chemotherapy. However, not all patient tumors respond to chemotherapy. The variable cytotoxic effects of chemotherapies may be due to how cancer cells regulate reactive oxygen species (ROS). In this study, we examined two mouse breast cancer cell lines: 4T1 and EO771, vary when treated with hydrogen peroxide (H2O2) and 5-Fluorouracil (5FU), known ROS-inducing substances. In 4T1 cells H2O2 increased oxidized DNA but caused minimal cell death. While in EO771 cells that same amount of H2O2 caused complete apoptosis. Cell number, ROS, and cell death showed a dose-dependent connection between 4T1 cells and increased 5FU concentrations. Additionally, the EO771 cells had a dose threshold at 0.01mM in which greater concentrations lowered cell number but did not always increase cell death. Both ROS-inducing treatments suggest cell lines have varying capacities for ROS. To determine how cells defend against oxidative stress we examined the expression of the novel antioxidant enzyme Methionine Sulfoxide Reductase b3 (Msrb3).The gene amplification of MsrB3 measured by qPCR, demonstrated basal MsrB3 expression is higher in 4T1 cells compared to EO771. Additionally, relative gene expression after 5FU treatment concluded that 4T1 cells increase the antioxidant gene expression, heme-oxygenase 1 (HO-1), and may have the ability to increase MsrB3 while EO771 cells cannot. Overall, this difference suggests that EO771 cells are susceptible to 5FU treatment while 4T1 cells are more resistant because they can better regulate oxidative stress.

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