Equol Induces Mitochondria-mediated Apoptosis of Human Cervical Cancer Cells

Abstract

Background/Aim: The present study aimed to investigate anticancer properties of equol and demonstrate its underlying mechanisms of action in human cervical cancer HeLa cells. Materials and Methods: Inhibition of cell viability was examined by 3-(4,5-dimethylthiazoly-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was evaluated by observation of apoptotic cell morphology, and an increase of annexin-V⁺ cells. Western blotting was used to examine apoptosis-related proteins. Flow cytometry was used to measure mitochondrial membrane potential (MMP) and reactive oxygen species (ROS). Results: Equol treatment inhibited HeLa cell proliferation in dose- and time-dependent manner. Equol-induced apoptotic cell death was accompanied by the activation of caspases, and alteration of MMP and mitochondrial membrane proteins; equol also rapidly triggered ROS production. Pre-treatment with N-acetylcysteine blocked loss of MMP, caused increase of Bcl-2-associated X protein (Bax)/B-cell lymphoma 2 (Bcl-2) ratio, caspase-8 activation, and apoptosis induced by equol. Conclusion: Equol is a potential anticancer agent against HeLa, with possible mechanisms involved in ROS generation and mitochondrial membrane alteration.