Inhibition of Human Breast Cancer Cell Growth and Enzymatic Activity by a Fermented Nutraceutical

Abstract

Human breast cancer cell lines MCF-7 (ER-positive) and Hs578T (ER-negative) were cultured and one lot incubated for 48 h with 5-50 mug/ml of a fermented phytocompound (MK: Manda-Koso, Innoshima, Japan). In vitro, it appeared a dose-dependent decrease of cell viability (5-57%) in MK group in both cell lines (P < 0.001, plateau: 30 microg/ml), decreased beta-galactosidase activity, enhanced apoptosis, and inversely increased Bax/Bcl2 ratio (P < 0.01) with an upregulation of p53 (P < 0.05). In the in vivo model, Balb-c mice were inoculated with tumor cells and the treatment group was fed with 20 mg of MK. Tumor weight in MK-fed group was time-course reduced by 22% to 51% at 2 and 4 weeks, respectively (P < 0.05) with increased survival (P < 0.05). Tumour tissue of MK-fed mice showed a downregulated Bcl-2 with increased Bax/Bcl-2 ratio, reduced PCNA, and activated caspase 3. Although more studies are ongoing to foster the clinical applicability of MK integrated within a rational chemopreventive and therapeutic strategy, a p53-mediated mechanism is likely to play a relevant role, besides its reported antioxidant capacity, NK cell activity enhancement, cancer-cytostatic activity properties.