Euxanthone inhibits glycolysis and triggers mitochondria-mediated apoptosis by targeting hexokinase 2 in epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is one of the most prevalent gynaecological cancers. Euxanthone, an active ingredient of the medicinal plant Polygala caudata, exhibits a selective cytotoxic effect in tumour cells. The present study was aimed to determine whether euxanthone could suppress ovarian tumour growth, and to study the relevant mechanism. Two EOC cell lines, SKOV3 and A2780, were used as the in vitro model and treated with euxanthone. Cell viability and apoptosis were assayed using Cell Counting Kit-8 (CCK-8) and Annexin-V FITC/PI staining, respectively. Commercially available kits were used to measure the glucose consumption, lactate production, and intracellular ATP levels. Western blots assay was conducted to examine the level of apoptotic markers. To examine the roles of HK2 and STAT3 in the anti-tumour effect of euxanthone, cells were transfected with vectors overexpressing HK2 or STAT3, and assayed as above. Finally, SKOV3 cells were injected to mice models to appreciate the anti-neoplastic effect of euxanthone in vivo. We found that euxanthone impaired the cell viability and induced apoptosis via the intrinsic pathway in a concentration-dependent fashion in both SKOV3 and A2780 cells. Euxanthone also caused inhibition of glycolysis. Apoptosis and glycolysis inhibition was mediated by the downregulation of HK2, which in turn was a result of STAT3 inactivation. In vivo experiments also supported that euxanthone could exert anti-cancer activities without general toxicity. In conclusion, euxanthone triggered mitochondrial apoptosis and inhibited glycolysis in EOC cells.

SIGNIFICANCE OF THE STUDY: Euxanthone triggered mitochondrial apoptosis and inhibited glycolysis in EOC cells. Our findings provide preliminary experimental data that support further studies on the potential therapeutic role of euxanthone in ovarian cancer.