Tormentic acid in foods exerts anti-proliferation efficacy through inducing apoptosis and cell cycle arrest

Tormentic acid (TA) is a triterpenoid saponin widely distributed in natural plant foods with various bioactivities. However, the underlying pathways through which TA exerts the bioactivities remain unclear. Here, experiments were carried out to elucidate the molecular mechanisms accounting for the antiproliferation of TA using MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay, flow cytometry, quantitative real-time polymerase chain reaction and Western blotting analysis. TA exhibited a dose-dependent inhibitory effect on MCF-7 cells, which was caused by apoptosis and G0/G1 phase arrest. Reactive oxygen species (ROS) acts as an upstream mediator in TA-induced MCF-7 cell growth inhibition and intracellular ROS levels induced mitochondrial dysfunction, thereby resulting in the release of apoptogenic factors into cytosol, and then activating caspase-3 and caspase-9. TA induced cell cycle arrest via changing the cyclin D1 and cyclin-dependent kinase 4 messenger ribonucleic acid expression levels. Moreover, TA significantly down-regulated the NF-kappa-B cell survival pathway and the expression level of phosphorylated ERK. (C) 2015 Elsevier Ltd. All rights reserved.