Advisory Committee Chair
Trygve Tollefsbol
Document Type
Dissertation
Date of Award
2024
Degree Name by School
Doctor of Philosophy (PhD) College of Arts and Sciences
Abstract
Breast cancer (BC) is a widespread malignancy that, despite advancements in treatments and improvements in survival, had an estimated 297,790 new cases and 43,170 mortalities in 2023. With around 1 in every 8 women in the US expected to be diagnosed with BC at some point in their lives, the economic, societal, and healthcare burdens associated with this disease cannot be understated. Because of this, treatments and preventions that are affordable, efficacious, and easily administered are in high demand. Preventive therapies have shown great promise in reducing disease burden with relatively few serious side effects. BC prevention through the consumption of epigenetically active plant-based compounds known as dietary phytochemicals (DP) has become a large area of research due to their potency, relative low cost, and little to no side effects. However, questions remain as to the best timeline of administration and mechanisms of action for many phytochemicals. Our studies aimed to address these questions for the phytochemicals sulforaphane (SFN) and withaferin a (WFA), respectively. Our results indicate that SFN-containing broccoli sprout extract administered during the peripubertal period may be important for later-life BC prevention and that decreases in promoter methylation of the tumor suppressor gene p21 and resulting p53-independent increases in its gene expression may be vital for the anticancer function of WFA. These results indicate that puberty may be a critical period for the effective administration of phytochemicals and an important time to target for the prevention of breast cancer. These results also suggest that WFA may have value in the prevention of highly prevalent and pathogenic p53-mutant BC.
Recommended Citation
Brane, Andrew, "Temporal And Epigenetic Mechanisms Underlying Dietary Phytochemicals In Breast Cancer Prevention" (2024). All ETDs from UAB. 3886.
https://digitalcommons.library.uab.edu/etd-collection/3886