Schizandrin A inhibits cellular phenotypes of breast cancer cells by repressing miR-155.

Abstract

Schizandrin A (SchA) is a type of lignan with biological properties against oxidation, inflammation, and cancer. Here, we aimed to sustain the bioactive properties of SchA in proliferative and motional phenotypes of MDA-MB-231 cells and their molecular mechanism. MDA-MB-231 cells were exposed to SchA. At 24 h after SchA treatment, the viability and proliferation were measured using CCK-8 and BrdU incorporation methods, respectively. Propidium iodide/Annexin V-FITC staining was carried out for detecting apoptotic cells. Migration and invasion were detected by 24-Transwell assay. Proteins expression was evaluated by Western blotting. MDA-MB-231 cells were transfected with microRNA (miR)-155 mimic, and miR-155 was detected by qRT-PCR. SchA weakens the viability of MDA-MB-231 cells in a dose-relative way (0-40 μM). Furthermore, 30 μM SchA significantly suppresses proliferation, enhances apoptosis, and inhibits migration and invasion. SchA strikingly decreases miR-155. Exogenous miR-155 counteracts the inhibitory effects that SchA confers on proliferative and motional activities. Finally, SchA was observed to blunt PI3K/AKT and Wnt/β-catenin while miR-155 mimic reverses the effects. Taken together, SchA downregulates miR-155 and results in the suppression of proliferation and motility in breast cancer cells. Our findings proposed that SchA might be used as an underlying therapeutic agent.