Suppression of Proliferation and Invasive Behavior of Human Metastatic Breast Cancer Cells by Dietary Supplement BreastDefend

Abstract

Aim: The study was to evaluate the effect of the dietary supplement BreastDefend (BD) on the proliferation and invasive behavior of highly metastatic human breast cancer cells in vitro. Methods: Cell proliferation and cytotoxicity of BD was evaluated in MDA-MB-231 cells treated with BD (0-40 μg/mL) by MTT assay and trypan blue staining, respectively. Expression of cell cycle regulatory genes were determined by DNA-microarray analysis. Effect of BD on invasiveness was assessed by cellular adhesion, migration, and invasion assays. Results: BD treatment of cells MDA-MB-231 resulted in the cytostatic inhibition of cell proliferation with IC₅₀ 22.2, 19.1, and 17.5 μg/mL for 24, 48, and 72 hours, respectively. The inhibition of proliferation was mediated by the upregulation expression of CCNG1, CHEK1, CDKN1C, GADD45A, and E2F2, whereas BD downregulated expression of CCNA1 and CDK6 genes. The induction of expression of GADD45A and inhibition of expression of cyclin A1 (gene CCNA1) by BD was also confirmed on the protein level. BD treatment suppressed the invasive behavior of MDA-MB-231 cells by the inhibition of cellular adhesion, migration, and invasion. This inhibition of invasiveness was mediated by the suppression of secretion of urokinase plasminogen activator (uPA), and by the downregulation of expression of CXCR4 in breast cancer cells treated with BD. Conclusion: BD inhibits proliferation and invasive behavior of the highly metastatic human breast cancer cells in vitro. BD may have a therapeutic potential for prevention or treatment of highly metastatic breast cancers.