title: β-D-glucan inhibits endocrine-resistant breast cancer cell proliferation and alters gene expression.
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.
authors.affiliation: Center of Biotechnology, Agricultural Research Directorate, Ministry of Science and Technology, Baghdad, Iraq.
authors.forename: Zainab M T
authors.initials: ZM
authors.lastname: Jafaar
authors.affiliation: Department of Biochemistry and Molecular Biology, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292, USA.
authors.forename: Lacey M
authors.initials: LM
authors.lastname: Litchfield
authors.affiliation: Department of Biochemistry and Molecular Biology, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292, USA.
authors.forename: Margarita M
authors.initials: MM
authors.lastname: Ivanova
authors.affiliation: Department of Biochemistry and Molecular Biology, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292, USA.
authors.forename: Brandie N
authors.initials: BN
authors.lastname: Radde
authors.affiliation: Department of Biochemistry and Molecular Biology, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292, USA.
authors.forename: Numan
authors.initials: N
authors.lastname: Al-Rayyan
authors.affiliation: Department of Biochemistry and Molecular Biology, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292, USA.
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Klinge
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000096:biosynthesis; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis; D061986:MCF-7 Cells; D051266:Nuclear Respiratory Factor 1 / Q000096:biosynthesis / Q000235:genetics; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy*; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis; D051176:beta Catenin / Q000096:biosynthesis; D047071:beta-Glucans / Q000494:pharmacology*
chemical_list: C495270:CTNNB1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; C495633:NRF1 protein, human; D051266:Nuclear Respiratory Factor 1; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins; D051176:beta Catenin; D047071:beta-Glucans