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 journalArticle

155 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Curcumin
Oxidation-Reduction
Apoptosis
Cell Cycle Checkpoints
Neoplasms
Thioredoxins
Mitochondrial Membrane Potential
Phosphatidylserines
Caspase 3
Colonic Neoplasms
Glutathione
Prostatic Neoplasms
Cell Cycle
Cell Count
Breast Neoplasms
Cell Line
DNA

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

  • Pharmacology
  • Cancer Research
  • Oncology

Cite this

EF24, a novel synthetic curcumin analog, induces apoptosis in cancer cells via a redox-dependent mechanism. / Adams, Brian K.; Cai, Jiyang; Armstrong, Jeff; Herold, Marike; Lu, Yang J.; Sun, Aiming; Snyder, James P.; Liotta, Dennis C.; Jones, Dean P.; Shoji, Mamoru.

In: Anti-Cancer Drugs, Vol. 16, No. 3, 03.2005, p. 263-275.

Research output: Contribution to journalArticle

Adams, BK, Cai, J, Armstrong, J, Herold, M, Lu, YJ, Sun, A, Snyder, JP, Liotta, DC, Jones, DP & Shoji, M 2005, 'EF24, a novel synthetic curcumin analog, induces apoptosis in cancer cells via a redox-dependent mechanism', Anti-Cancer Drugs, vol. 16, no. 3, pp. 263-275. https://doi.org/10.1097/00001813-200503000-00005
Adams, Brian K. ; Cai, Jiyang ; Armstrong, Jeff ; Herold, Marike ; Lu, Yang J. ; Sun, Aiming ; Snyder, James P. ; Liotta, Dennis C. ; Jones, Dean P. ; Shoji, Mamoru. / EF24, a novel synthetic curcumin analog, induces apoptosis in cancer cells via a redox-dependent mechanism. In: Anti-Cancer Drugs. 2005 ; Vol. 16, No. 3. pp. 263-275.
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