Journal
TOXICOLOGY IN VITRO
Volume 26, Issue 4, Pages 585-594Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2012.02.003
Keywords
Apoptosis; Cytotoxicity; DNA sensors; Nitroquinone; Nor-beta-lapachone; Bioelectrochemistry
Categories
Funding
- CNPq
- IM-INOFAR
- MCT/CNPq/MS/Neoplasias
- RENORBIO
- BNB
- CAPES/COFECUB
- PROCAD/NF
- PRONEX-FAPERJ [E-26/110.574/2010]
- PRONEX-FAPEAL
- FAP-EMIG [APQ-04166-10]
- INCT-Bioanalitica
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In this study, the cytotoxicity, genotoxicity and early ROS generation of 2,2-dimethyl-(3H)-3-(N-3'-nitrophenylamino)naphtho[1,2-b]furan-4,5-dione (QPhNO(2)) were investigated and compared with those of its precursor, nor-beta-lapachone (nor-beta), with the main goal of proposing a mechanism of antitumor action. The results were correlated with those obtained from electrochemical experiments held in protic (acetate buffer pH 4.5) and aprotic (DMF/TBABF(4)) media in the presence and absence of oxygen and with those from dsDNA biosensors and ssDNA in solution, which provided evidence of a positive interaction with DNA in the case of QPhNO(2). QPhNO(2) caused DNA fragmentation and mitochondrial depolarization and induced apoptosis/necrosis in HL-60 cells. Pre-treatment with N-acetyl-L-cysteine partially abolished the observed effects related to the QPhNO(2) treatment, including those involving apoptosis induction, indicating a partially redox-dependent mechanism. These findings point to the potential use of the combination of pharmacology and electrochemistry in medicinal chemistry. (C) 2012 Elsevier Ltd. All rights reserved.
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