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Oxidative Medicine and Cellular Longevity
Volume 2015 (2015), Article ID 495305, 10 pages
Research Article

DNA Damage and Inhibition of Akt Pathway in MCF-7 Cells and Ehrlich Tumor in Mice Treated with 1,4-Naphthoquinones in Combination with Ascorbate

1Laboratório de Bioquímica Experimental, Departamento de Bioquímica, Universidade Federal de Santa Catarina, Florianópolis, Brazil
2Programa de Pós-Graduação em Ciências da Saúde da Universidade do Sul de Santa Catarina (UNISUL), SC, Brazil
3Departamento de Ciencias Químicas y Farmacéuticas, Universidad Arturo Prat, 2120 Avenida Arturo Prat, Iquique, Chile
4Toxicology and Cancer Biology Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, 73 Avenue E. Mounier, GTOX 7309, 1200 Brussels, Belgium

Received 29 November 2014; Revised 19 January 2015; Accepted 19 January 2015

Academic Editor: Ryuichi Morishita

Copyright © 2015 Fabiana Ourique 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.


The aim of this study was to enhance the understanding of the antitumor mechanism of 1,4-naphthoquinones and ascorbate. Juglone, phenylaminonaphthoquinone-7, and 9 (Q7/Q9) were evaluated for effects on CT-DNA and DNA of cancer cells. Evaluations in MCF-7 cells are DNA damage, ROS levels, viability, and proliferation. Proteins from MCF-7 lysates were immunoblotted for verifying PARP integrity, γH2AX, and pAkt. Antitumor activity was measured in Ehrlich ascites carcinoma-bearing mice. The same markers of molecular toxicity were assessed in vivo. The naphthoquinones intercalate into CT-DNA and caused oxidative cleavage, which is increased in the presence of ascorbate. Treatments caused DNA damage and reduced viability and proliferation of MCF-7 cells. Effects were potentiated by ascorbate. No PARP cleavage was observed. Naphthoquinones, combined with ascorbate, caused phosphorylation of H2AX and inhibited pAkt. ROS were enhanced in MCF-7 cells, particularly by the juglone and Q7 plus ascorbate. Ehrlich carcinoma was inhibited by juglone, Q7, or Q9, but the potentiating effect of ascorbate was reproduced in vivo only in the cases of juglone and Q7, which caused up to 60% inhibition of tumor and the largest extension of survival. Juglone and Q7 plus ascorbate caused enhanced ROS and DNA damage and inhibited pAkt also in Ehrlich carcinoma cells.