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Int J Mol Sci. 2018 Jul 27;19(8). pii: E2204. doi: 10.3390/ijms19082204.

Combinational Proanthocyanidins and Resveratrol Synergistically Inhibit Human Breast Cancer Cells and Impact Epigenetic⁻Mediating Machinery.

Gao Y1, Tollefsbol TO2,3,4,5,6.

Author information

1
Department of Biology, University of Alabama at Birmingham, 1300 University Boulevard, Birmingham, AL 35294, USA. mvgold@uab.edu.
2
Department of Biology, University of Alabama at Birmingham, 1300 University Boulevard, Birmingham, AL 35294, USA. trygve@uab.edu.
3
Comprehensive Center for Healthy Aging, University of Alabama Birmingham, 1530 3rd Avenue South, Birmingham, AL 35294, USA. trygve@uab.edu.
4
Comprehensive Cancer Center, University of Alabama Birmingham, 1802 6th Avenue South, Birmingham, AL 35294, USA. trygve@uab.edu.
5
Nutrition Obesity Research Center, University of Alabama Birmingham, 1675 University Boulevard, Birmingham, AL 35294, USA. trygve@uab.edu.
6
Comprehensive Diabetes Center, University of Alabama Birmingham, 1825 University Boulevard, Birmingham, AL 35294, USA. trygve@uab.edu.

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.

KEYWORDS:

breast cancer; epigenetics; grape seed proanthocyanidins; resveratrol; synergism

PMID:
30060527
PMCID:
PMC6121898
DOI:
10.3390/ijms19082204
[Indexed for MEDLINE]
Free PMC Article

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