EF24, a novel synthetic curcumin analog, induces apoptosis in cancer cells via a redox-dependent mechanism

In this study, we show that the novel synthetic curcumin analog, EF24, induces cell cycle arrest and Apoptosis by means of a redox-dependent mechanism in MDA-MB-231 human breast Cancer cells and DU-145 human prostate Cancer cells. Cell cycle analysis demonstrated that EF24 causes a G2/M arrest in both cell lines, and that this cell cycle arrest is followed by the induction of Apoptosis as evidenced by Caspase-3 activation, phosphatidylserine externalization and an increased number of cells with a sub-G1 DNA fraction. In addition, we demonstrate that EF24 induces a depolarization of the mitochondrial membrane potential, suggesting that the compound may also induce Apoptosis by altering mitochondrial function. EF24, like curcumin, serves as a Michael acceptor reacting with glutathione (GSH) and thioredoxin 1. Reaction of EF24 with these agents in vivo significantly reduced intracellular GSH as well as oxidized GSH in both the wild-type and Bcl-xL overexpressing HT29 human colon Cancer cells. We therefore propose that the Anticancer effect of a novel curcumin analog, EF24, is mediated in part by redox-mediated induction of Apoptosis.