Attenuation of the stem cell properties and the oxidative phosphorylation by ampelopsin in therapy-resistant MDA-MB-231 breast cancer cells.

Abstract

Cancer stem cells (CSCs) have an important function in tumorigenesis and therapy resistance. Therefore, targeting CSCs is a prominent therapeutic option for triple negative breast cancer (TNBC) treatment. Ampelopsin, a major substance found in Ampelopsis species, could prevent the proliferation, colony formation ability as well as trigger apoptosis at dose-dependent manners in resistant MDA-MB-231/IR cells that are enrichment of stem-like characteristics. Importantly, ampelopsin exerted the inhibitory ability on the stem cell profiling of MDA-MB-231/IR cells, as represented by the results of mammosphere formation, CD44+/CD24- population, aldehyde dehydrogenase (ALDH) population and the levels of well-known stemness markers. Moreover, ampelopsin inhibited the epithelial–mesenchymal transition (EMT) transition, as evidenced by a dramatically reduction of migration, invasive capacity and the levels of mesenchymal markers – Snail, Slug and MMP2 and a rise of epithelial marker – E-cadherin. Notably, ampelopsin dramatically diminished oxidative phosphorylation which reflected mitochondrial function, as represented by a decrease of oxygen consumption rate and adenosine triphosphate level in resistant MDA-MB-231/IR cells. Interestingly, NF-ĸB signaling pathways was suppressed after ampelopsin treatment, displayed by the declines of IκBα and p65 phosphorylation, as well as the NF-κB activation stimulated by tumor necrosis factor (TNF)-α treatment. These findings illustrated that ampelopsin acts as a TNF-α/NF-κB axis inhibitor in breast cancer stem cells.