Licochalcone a inhibits cellular motility by suppressing E-Cadherin and MAPK signaling in Breast Cancer

Abstract

A compound isolated from Glycyrrhiza uralensis, licochalcone A (LA) exhibits anti-inflammatory and anti-tumor properties in various cell lines. LA has been found to promote autophagy and suppress specificity protein 1, inducing apoptosis in breast cancer cells. However, the regulation of breast cancer cell invasion and migration by LA is elusive. Thus, the present study investigated whether LA induces apoptosis and cellular motility in MDA-MB-231 breast cells, and investigated the underlying molecular mechanisms. MDA-MB-231 cells treated with LA and cell viability measured by cell counting kit-8 assay. Apoptotic signal proteins checked by flow cytometry, fluorescent staining, and Western blot. LA effectively suppressed cell migration, and modulated E-cadherin and vimentin expression by blocking MAPK and AKT signaling. LA inhibited cell proliferation and cell cycle, modulated mitochondrial membrane potential and DNA damage, and reduced oxidative stress in MDA-MB-231 cells. LA also activated cleaved-caspase 3 and 9, significantly decreased Bcl-2 expression, ultimately causing the release of cytochrome c from the mitochondria into the cytoplasm. Overall, our findings suggest that LA decreases cell proliferation and increases reactive oxygen species production for induced apoptosis, and regulates E-cadherin and vimentin by reducing MAPK and AKT signaling, resulting in suppressed MDA-MB-231 cell migration and invasion.