SUPPRESSION OF PROLIFERATION AND INCREASED OF PRO-APOPTOTIC PROTEINS EXPRESSION IN HUMAN BREAST CANCER CELLS AFTER THEIR CO-CULTIVATION WITH BIFIDOBACTERIUM ANIMALIS IN VITRO

Abstract

Summary. Aim: to determine the viability, proliferative activity, and reactive oxygen species (ROS) production in human breast cancer (BC) cells after their co-cultivation with a human microbiota member Bifidobacterium animalis. Object and methods: the study was conducted in vitro on human BC cells of MCF7, T47D, and MDA-MB-231 lines. Cells were co-cultured with live B. animalis bacteria in direct or metabolite-mediated (contactless co-cultivation in the Insert system) interaction between eukaryotic and bacterial cells. ROS production was assessed by flow cytometry. The expression of proteins associated with the regulation of proliferation and apoptosis in BC cells was evaluated by immunocytochemical analysis. Results: The most pronounced changes in the growth characteristics of human BC cells in vitro are caused by the direct interaction of bacterial and malignant cells, compared to the bacterial metabolite-mediated action. MCF-7 cells of the luminal subtype are most sensitive to the effects of B. animalis. Co-cultivation of BC cells with B. animalis leads to a decrease of Ki-67 expression in malignant cells, an increase in ROS production, and the expression of pro-apoptotic proteins Bax and p21WAF1. Translocalization of p21WAF1 expression from the cytoplasm to the cell nucleus was detected in T47D cells after exposure to B. animalis. Conclusions: the interaction of human BC cells with B. animalis and their secreted metabolites led to inhibition of the malignant cells proliferation, induction of oxidative stress, and apoptosis program activation in BC cells.