期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 19, 期 23, 页码 7057-7062出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2011.10.005
关键词
Dimeric naphthoquinones; Anticancer agents; Cytotoxicity; Oxidative stress; Tumor metabolism
资金
- Johns Hopkins Hospital Department of Pathology
- Richard Starr Ross Clinician Scientist Award
- National Institute of Health [AI43687]
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 mu M. 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. (C) 2011 Elsevier Ltd. All rights reserved.
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