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Journal of Amino Acids
Volume 2013 (2013), Article ID 509056, 7 pages
http://dx.doi.org/10.1155/2013/509056
Research Article

DTNQ-Pro, a Mimetic Dipeptide, Sensitizes Human Colon Cancer Cells to 5-Fluorouracil Treatment

1Department of Pharmaceutical and Toxicological Chemistry, University of Naples Federico II, Naples, Italy
2Department of Pharmaceutical Sciences, University of Salerno, Fisciano, Salerno, Italy
3Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy
4Italian Institute for Auxology, IRCC, 20145 Milan, Italy

Received 1 February 2013; Accepted 27 March 2013

Academic Editor: Giuseppe De Rosa

Copyright © 2013 Isabel Gomez-Monterrey et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The resistance of growing human colon cancer cells to chemotherapy agents has been correlated to endogenous overexpression of stress proteins including the family of heat shock proteins (HSPs). Previously, we have demonstrated that a quinone-based mimetic dipeptide, named DTNQ-Pro, induced differentiation of growing Caco-2 cells through inhibition of HSP70 and HSP90. In addition, our product induced a HSP27 and vimentin intracellular redistribution. In the present study, we have evaluated whether a decrease of stress proteins induced by DTNQ-Pro in Caco-2 cells could sensitize these cells to treatment with 5-fluorouracil (5-FU) cytotoxicity. The pretreatment of Caco-2 with 500 nM of DTNQ-Pro increases lipid peroxidation and decreases expression of p38 mitogen-activated protein kinase (MAPK) and FOXO3a. At the same experimental conditions, an increase of the 5-FU-induced growth inhibition of Caco-2 cells was recorded. These effects could be due to enhanced DTNQ-Pro-induced membrane lipid peroxidation that, in turn, causes the sensitization of cancer cells to the cytotoxicity mediated by 5-FU.