By Loren Delgadillo Llano, Briza Valdes-Llamas, Wagma Zaki

Faculty Mentor: Laura Sipe

Abstract

Triple negative breast cancer (TNBC) is an aggressive subtype that is difficult to treat, resulting in a 66% 5-year survival rate for regional invasion to nearby structures or lymph nodes. This creates an importance to researching the various chemotherapy efficacy methods on the TNBC viability/cellular apoptosis. One possible method of increasing treatment efficacy is methionine restriction. Methionine is an essential amino acid important for making proteins. Cancer cells often exhibit higher methionine dependency compared to normal cells; by restricting methionine, it’s possible to selectively target cancer cells while sparing normal cells and potentially enhance the efficacy of chemotherapy. The experiment involved two types of TNBC cells, E0771 and 4T1. Cancer cells were treated with either 4% methionine restriction or complete media, and the cell proliferation over time was measured. It was determined that the cell count decreased for both cells lines treated with 4% methionine restriction compared to complete media, suggesting methionine restriction inhibits cancer growth. In the E0771 cell line, the complete media had a linear increase in proliferation over 72 hours, while the 4% methionine restriction presented a flat line. The lack of proliferation with the 4% methionine restriction could be due to cells remaining in the G0, resting phase. Conversely, the complete media 4T1 cell line, the control increased steadily until the 50-hour mark where it began to plateau. The 4% methionine restriction exhibited an increase during the first 24 hours, however, the cell count started to decrease in the 48 and 72-hour mark. The decrease in cell count could be due to cell death.

Methionine restriction was tested in combination with two chemotherapies, 5-Fluorouracil (5FU) and cisplatin. The effects of methionine restriction alongside a 5FU treatment show an apparent lack of synergism between the methionine restriction and 5FU combo. However, in combination with cisplatin, methionine restricted cells were more sensitive. Overall, methionine restriction shows differential effects across cell lines and across chemotherapies. This research is important to understand treatment strategies across patients.