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

Brian K. Adams, Jiyang Cai, Jeff Armstrong, Marike Herold, Yang J. Lu, Aiming Sun, James P. Snyder, Dennis C. Liotta, Dean P. Jones, Mamoru Shoji

Research output: Contribution to journalArticlepeer-review

158 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)263-275
Number of pages13
JournalAnti-Cancer Drugs
Volume16
Issue number3
DOIs
StatePublished - Mar 2005

Keywords

  • Apoptosis
  • Caspase
  • DNA fragmentation
  • EF24
  • G/M cell cycle arrest
  • Glutathione
  • Mitochondrial membrane depolarization
  • Oxidized glutathione
  • Phosphatidylserine externalization
  • Reactive oxygen species
  • Reduction-oxidation (redox)

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Cancer Research

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