All ETDs from UAB

Advisory Committee Chair

Trygve O Tollefsbol

Advisory Committee Members

Asim K Bej

Yuanyuan Li

Christine Skibola

Thane Wibbels

Document Type

Dissertation

Date of Award

2018

Degree Name by School

Doctor of Philosophy (PhD) College of Arts and Sciences

Abstract

Breast cancer is the second most common cancer and the second leading cause of death from cancer among women in the United States. Cancer prevention and therapy through use of phytochemicals that have epigenetic properties has gained considerable popularity during the past few decades. Such dietary components include but are not limited to grape seed proanthocyanidins (GSPs), resveratrol (Res) and sulforaphane (SFN). Here we report for the first time that GSPs and Res in combination dose- and time-dependently inhibited cell viability and posttreatment colony forming ability synergistically in MDA-MB-231 and MCF-7 human breast cancer cells, while GSPs and SFN in combination antagonistically inhibited these two cell lines in a dose- and time-dependent manner. Additional analyses suggest that the synergism between GSPs and Res in MDA-MB-231 cells could be as a result of the enhancement of signal transmission in apoptosis as the combinational treatment with GSPs and Res synergistically up-regulated the expression of proapoptotic protein Bax and down-regulated the expression of antiapoptotic protein Bcl-2. In MCF-7 cells, however, Bax expression was greatly down-regulated by GSPs regardless of the presence of Res or SFN. Furthermore, DNA methyltransferase (DNMT) and histone deacetylase (HDAC) activity assays were conducted. The results show that the combinational treatment with GSPs and Res led to greater inhibition in DNMT and HDAC activities compared with treatment with either GSPs or Res alone in MDA-MB-231 and MCF-7 cells, whereas GSPs and SFN antagonistically inhibited DNMT and HDAC activities in both cell lines. These findings suggest that the synergism between GSPs and Res in MCF-7 cells and the antagonism between GSPs and SFN in both MDA-MB-231 and MCF-7 cells could be associated with the regulation of DNA methylation and/or histone modifications.

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