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

Oxidative Medicine and Cellular Longevity
Fabiana OuriqueR C Pedrosa

Abstract

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. Ju...Continue Reading

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Citations

Sep 28, 2016·Oxidative Medicine and Cellular Longevity·Javier PalaciosPedro Buc Calderon
Aug 24, 2019·Current Pharmaceutical Biotechnology·Islam M El-GarawaniEbtesam Nafie
Aug 28, 2018·Oxidative Medicine and Cellular Longevity·Javier PalaciosFredi Cifuentes
Nov 18, 2018·Toxins·Elena CatanzaroCarmela Fimognari
Apr 10, 2019·Antioxidants·Taseer Ahmad, Yuichiro J Suzuki
Nov 19, 2020·Oxidative Medicine and Cellular Longevity·Rumiana BakalovaTatsuya Higashi

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Methods Mentioned

BETA
electrophoresis
MDA

Software Mentioned

GraphPad Prism

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