Emd-D inhibited ovarian cancer progression via PFKFB4-dependent glycolysis and apoptosis

Ovarian cancer presents a significant challenge to women's health, demanding effective therapeutic approaches. Emd-D, a derivative of Emodin, exhibits improved pharmaceutical properties and bioavailability. Herein, CCK8 assays and Ki-67 staining revealed a dose-dependent inhibition of cell proliferation by Emd-D. Additionally, migration and invasion experiments confirmed its inhibitory effects on OVHM cells, while flow cytometry analysis demonstrated Emd-D-induced apoptosis. Further mechanistic investigations unveiled that Emd-D acts as an inhibitor by directly binding to the glycolysis-related enzyme PFKFB4. This was substantiated by alterations in intracellular lactate and pyruvate levels, as well as GLUT1 and HK2 expression. Overexpression experiments of PFKFB4 further supported the dependence of Emd-D on PFKFB4-mediated glycolysis, as well as the SRC3/mTORC1 pathway-associated apoptosis. In vivo experiments displayed reduced xenograft tumor sizes upon Emd-D treatment, along with suppressed glycolysis and increased expression of Bax/Bcl-2 apoptotic proteins within the tumors. In summary, our findings demonstrate that Emd-D holds potential as an anti-ovarian cancer agent through its inhibition of the PFKFB4-dependent glycolysis pathway and induction of apoptosis. These results provide a solid foundation for further exploration of Emd-D as a promising drug candidate for ovarian cancer treatment.