β-D-glucan inhibits endocrine-resistant breast cancer cell proliferation and alters gene expression

Jafaar,Zainab M.T.; Litchfield,Lacey M.; Ivanova,Margarita M.; Radde,Brandie N.; Al-Rayyan,Numan; Klinge,Carolyn M.

doi:10.3892/ijo.2014.2294

β-D-glucan inhibits endocrine-resistant breast cancer cell proliferation and alters gene expression

Authors:
- Zainab M.T. Jafaar
- Lacey M. Litchfield
- Margarita M. Ivanova
- Brandie N. Radde
- Numan Al-Rayyan
- Carolyn M. Klinge
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Affiliations: Center of Biotechnology, Agricultural Research Directorate, Ministry of Science and Technology, Baghdad, Iraq, Department of Biochemistry and Molecular Biology, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292, USA
Published online on: February 10, 2014 https://doi.org/10.3892/ijo.2014.2294
Pages: 1365-1375

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Abstract

Endocrine therapies have been successfully used for breast cancer patients with estrogen receptor α (ERα) positive tumors, but ~40% of patients relapse due to endocrine resistance. β-glucans are components of plant cell walls that have immunomodulatory and anticancer activity. The objective of this study was to examine the activity of β-D-glucan, purified from barley, in endocrine-sensitive MCF-7 versus endocrine-resistant LCC9 and LY2 breast cancer cells. β-D-glucan dissolved in DMSO but not water inhibited MCF-7 cell proliferation in a concentration-dependent manner as measured by BrdU incorporation with an IC50 of ~164±12 µg/ml. β-D-glucan dissolved in DMSO inhibited tamoxifen/endocrine-resistant LCC9 and LY2 cell proliferation with IC50 values of 4.6±0.3 and 24.2±1.4 µg/ml, respectively. MCF-10A normal breast epithelial cells showed a higher IC50 ~464 µg/ml and the proliferation of MDA-MB-231 triple negative breast cancer cells was not inhibited by β-D-glucan. Concentration-dependent increases in the BAX/BCL2 ratio and cell death with β-D-glucan were observed in MCF-7 and LCC9 cells. PCR array analysis revealed changes in gene expression in response to 24-h treatment with 10 or 50 µg/ml β-D-glucan that were different between MCF-7 and LCC9 cells as well as differences in basal gene expression between the two cell lines. Select results were confirmed by quantitative real-time PCR demonstrating that β-D-glucan increased RASSF1 expression in MCF-7 cells and IGFBP3, CTNNB1 and ERβ transcript expression in LCC9 cells. Our data indicate that β-D-glucan regulates breast cancer-relevant gene expression and may be useful for inhibiting endocrine-resistant breast cancer cell proliferation.

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