Advisor(s)

Trygve Tollefsbol

Committee Member(s)

Matthew Stoll
Melissa Harris
Mickie Powell
Yuanyuan Li

Document Type

Dissertation

Date of Award

6-4-2026

Degree Name

Doctor of Philosophy (PhD)

School

College of Arts and Sciences

Department

Biology

Abstract

Breast cancer (BC) accounts for 1 in 3 (or 30%) of all new female cancers each year and is the most common malignant cancer in women in the United States. Since the 1990s, there has been a 44% decrease in BC, but there is still a significant gap between certain groups in terms of mortality rates. Black women have a higher mortality rate and risk for triple-negative breast cancer (TNBC). This may be due to social (inadequate access to health care facilities, insurance, or completion of therapy) and biological (genetic mutations, tumor characteristics, or comorbidity) factors between races and other ethnic groups. Treatments for BC consist of surgery, chemotherapy, immunotherapy, radiation therapy, and hormonal therapy. There have also been studies to show different preventive measures and adjuvant strategies to reduce the risk of BC. Dietary compounds have been utilized for centuries to assist and prevent risk of BC development. Within our previous studies, we have identified the benefits of consuming sulforaphane (SFN), a phytochemical within common cruciferous vegetables, along with epigallocatechin-3- gallate (EGCG), a well-known antioxidant found in green tea. These two dietary compounds work synergistically to decrease the progression and tumor development of BC in vivo and in vitro. It is important to note that these components were investigated at early stages within the in vivo studies because our focus is centered around early life and preventive measures for BC development. Within our current studies, we have iii investigated the positions that metabolites and microbes have in BC development and prevention. The in vivo study utilized Faecalibaculum rodentinum, a Gram-positive bacterium that increased in relative abundance from 5% to 21% for the control versus the treatment groups. There was also a significant difference in tumor weight in the treatment group as compared to the control group. The in vitro study focused on the combinatorial impact of withaferin A (WA), a steroidal lactone, and sodium butyrate (NaB), a short?chain fatty acid (SCFA), on TNBC cell lines. We were able to identify the additive and synergistic abilities of the combinatorial group, decreasing the cellular viability of the BC cell lines, along with inhibiting epigenetic modifier targets and NF-κB signaling pathway components, through gene expression analysis. These investigations help illuminate how these dietary compounds and metabolites could play crucial roles in complementary treatment to known therapies for BC control and prevention. Keywords: Breast Cancer, Epigenetics, Faecalibaculum rodentinum, Sodium butyrate, Withaferin A, Metabolites, Treatments

Keywords

Breast cancer;Epigenetics;Faecalibaculum rodentinum;Metabolites;Sodium butyrate;Withaferin A

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