Metabolic and electrochemical mechanisms of dimeric naphthoquinones cytotoxicity in breast cancer cells

Ashkan Emadi, Anne Le, Cynthia J. Harwood, Kenneth W. Stagliano, Farin Kamangar, Ashley E. Ross, Charles R. Cooper, Chi V. Dang, Judith E. Karp, Milena Vuica-Ross

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Cancer cells reprogram their metabolism due to genetic alteration to compensate for increased energy demand and enhanced anabolism, cell proliferation, and protection from oxidative damage. Here, we assessed the cytotoxicity of three dimeric naphthoquinones against the glycolytic MCF-7 versus the oxidative MDA-453 breast carcinoma cell lines. Dimeric naphthoquinones 1 and 2 impaired MDA-453, but not MCF-7, cell growth at IC 50 = 15 μM. Significant increase in reactive oxygen species, decrease in oxygen consumption and ATP production were observed in MDA-453 cells but not in MCF-7 cell. These findings suggest that oxidative stress and mitochondrial dysfunction are mechanisms by which these agents exert their cytotoxic effects. Cyclic voltammetry and semi-empirical molecular orbital calculations further characterized the electrochemical behavior of these compounds. These results also suggest that dimeric naphthoquinones may be used to selectively target cancer cells that depend on oxidative phosphorylation for energy production and macromolecular synthesis.

Original languageEnglish (US)
Pages (from-to)7057-7062
Number of pages6
JournalBioorganic and Medicinal Chemistry
Issue number23
StatePublished - Dec 1 2011


  • Anticancer agents
  • Cytotoxicity
  • Dimeric naphthoquinones
  • Oxidative stress
  • Tumor metabolism

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


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