Anti-Stemness and Anti-Proliferative Effects of Cadmium on Bovine Mammary Epithelial Cells

Cadmium accumulation in the body can damage a variety of organs and impair their development and functions. In the present study, we investigated the effect of cadmium on the stemness and proliferation of normal bovine mammary epithelial cells (BMECs). Normal bovine mammary epithelial cells treated with cadmium chloride were assessed for the expression of stemness-related proteins and cell proliferation. Western blotting results found that exposure to different concentrations of cadmium (0, 1.25, 2.5, and 5 μm) for 48 h significantly increased Gli1 expression but unexpectedly decreased the expression of downstream stem cell-related proteins including BMI1, SOX2, and ALDH. However, we also observed that treatment with 5 μm cadmium for 48 h inhibited mammosphere formation using microscopy. In this study, cadmium exposure significantly reduced cell viability and mobility. Flow cytometry detection found that cadmium decreased the percentage of cells in the G0 phase but increased the percentage of cells in the S phase and the apoptosis rate. Furthermore, cadmium exposure significantly increased the levels of caspase-8, caspase-3, and PARP cleavage as assessed by western blotting. Our study uncovers a previously unrecognized role of cadmium in mammary cell stemness and suggests that cadmium may affect breast development by impairing normal stem cell self-renewal and inducing their apoptosis. Therefore, this study provides important scientific significance regarding whether heavy metal cadmium affects normal breast development.