Advisory Committee Chair
Trygve O Tollefsbol
Advisory Committee Members
Stephen Barnes
Vithal K Ghanta
Casey D Morrow
Mickie L Powell
Document Type
Dissertation
Date of Award
2018
Degree Name by School
Doctor of Philosophy (PhD) College of Arts and Sciences
Abstract
Breast cancer is a major cause of cancer death among women in the United States. Current methods of chemoprevention and therapy have cytotoxic effects and have several short-term and long-term side effects. Therefore, the use of natural dietary bioactive compounds has gained prominence as safe and effective agents of chemoprevention and therapy. Genistein (GE), an isoflavone found in soy products, has been shown to exhibit several anticancer properties, particularly as an epigenetic modifier. We have observed that GE has the ability to alter the gut microbiome of germ-free mice humanized with fecal transplants from breast cancer patients undergoing chemotherapy. We have also observed that supplementation with GE can reduce tumor volume, tumor weight and increase latency in mice with human microbiome compared to mice on a control diet. In addition, our in vitro and in vivo findings indicate that GE when used in combination with sulforaphane (SFN), an isothiocyanate from cruciferous vegetables, is much more effective in reducing the viability of breast cancer cells than when they are administered alone. We have demonstrated that the combination of GE and SFN down-regulates KLF4 levels which play an important role in breast cancer stem cell formation. GE and SFN also down-regulate hTERT, HDAC2 and HDAC3 levels which are known to act in concert with KLF4. In vivo studies in mice further strengthen our hypothesis, where mice fed the combination diet of GE and SFN-rich broccoli sprouts had increased tumor latency and significantly reduced tumor volume when compared to the mice on a control diet or single administration of GE or SFN. Collectively, our studies provide support for the role of bioactive dietary compounds, like GE and SFN, as safe and effective agents of chemoprevention and therapy.
Recommended Citation
Paul, Bidisha, "Effect Of Dietary Compounds In Epigenetic Modulation And Microbial Alteration And Their Roles In Breast Tumor Inhibition" (2018). All ETDs from UAB. 2685.
https://digitalcommons.library.uab.edu/etd-collection/2685