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.
Adams
Brian K
BK
Program in Molecular and Systems Pharmacology, Emory University, Atlanta, GA 30322, USA.
Cai
Jiyang
J
Armstrong
Jeff
J
Herold
Marike
M
Lu
Yang J
YJ
Sun
Aiming
A
Snyder
James P
JP
Liotta
Dennis C
DC
Jones
Dean P
DP
Shoji
Mamoru
M
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D003474:Curcumin / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D008297:Male; D010084:Oxidation-Reduction; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003474:Curcumin