Abstract
Breast cancer is the second most common cancer and the second leading cause of death from cancer among women in the United States (US). Cancer prevention and therapy through the use of phytochemicals that have epigenetic properties has gained considerable interest during the past few decades. Such dietary components include, but are not limited to, grape seed proanthocyanidins (GSPs) and resveratrol (Res), both of which are present in red wine. In this study, we report for the first time the synergistic effects of GSPs and Res on inhibiting MDA-MB-231 and MCF-7 human breast cancer cells. Our results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays and clonogenic assays indicate that treatments with the combinations of GSPs and Res synergistically decreased cell viability and posttreatment cell proliferation in both cell lines. Additional analyses show that treatments with GSPs and Res in combination synergistically induced apoptosis in MDA-MB-231 cells by upregulating Bax expression and down-regulating Bcl-2 expression. DNA methyltransferase (DNMT) activity and histone deacetylase (HDAC) activity were greatly reduced in MDA-MB-231 and MCF-7 cells after treatments with GSPs and Res in combination. Collectively, our findings suggest that GSPs and Res synergistically inhibit human breast cancer cells through inducing apoptosis, as well as modulating DNA methylation and histone modifications.
Highlights
Breast cancer is the second most common cancer and the most common invasive cancer among women in the United States (US)
The treatments with Grape seed proanthocyanidins (GSPs) resulted in significant decreases in cell viability by 9% to 19% (p < 0.05) after 48 h and 30% to 41% (p < 0.05) after 72 h in MDA-M31B(A-2)3a1nd(AM) CaFn-d7 (MB)-231 cells, 13% to 35% (p < 0.05) after 48 h and 28% to 44% (p < 0.05) after 72 h in MCF-7 cells
The treatments with GSPs and Res in combinations resulted in a significant decrease in cell viability by 44% to 79% (p < 0.05) after 48 h and 69% to 90% (p < 0.05) after 72 h in MDA-MB-231 cells, 41% to 77% (p < 0.05) after 48 h and 77% to 91% (p < 0.05) after 72 h in MCF-7 cells
Summary
Breast cancer is the second most common cancer and the most common invasive cancer among women in the United States (US). 3,5,4’-trihydroxy-trans-stilbene or resveratrol (Res) is a stilbenoid, a polyphenol, as well as a phytoalexin naturally produced by a number of plants, such as grapes, berries, peanuts, and the roots of Japanese knotweed when under attack by pathogens It is most abundant in the skin of red grapes; it is rich in red wine [13,14]. The effect of GSPs and Res in combination on cancer, remains elusive To investigate this effect along with the underlying mechanisms at the molecular level, the estrogen receptor-negative (ER-), progesterone receptor-negative (PR-), and HER2-negative (HER2-) MDA-MB-231 human breast cancer cells and the ER+, PR+, and HER2-MCF-7 human breast cancer cells were selected for this study. We sought to examine the combined effects and mechanisms of these dietary components on breast cancer cells in humans
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