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High-Throughput 2018, 7(2), 12; https://doi.org/10.3390/ht7020012

Reactive Chemicals and Electrophilic Stress in Cancer: A Minireview

Faculté de Pharmacie, Faculté des Sciences et des Techniques, IICiMed, Université de Nantes, 2 rue de la Houssinière, 44322 Nantes, France
Received: 3 March 2018 / Revised: 19 April 2018 / Accepted: 26 April 2018 / Published: 27 April 2018
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Abstract

Exogenous reactive chemicals can impair cellular homeostasis and are often associated with the development of cancer. Significant progress has been achieved by studying the macromolecular interactions of chemicals that possess various electron-withdrawing groups and the elucidation of the protective responses of cells to chemical interventions. However, the formation of electrophilic species inside the cell and the relationship between oxydative and electrophilic stress remain largely unclear. Derivatives of nitro-benzoxadiazole (also referred as nitro-benzofurazan) are potent producers of hydrogen peroxide and have been used as a model to study the generation of reactive species in cancer cells. This survey highlights the pivotal role of Cu/Zn superoxide dismutase 1 (SOD1) in the production of reactive oxygen and electrophilic species in cells exposed to cell-permeable chemicals. Lipophilic electrophiles rapidly bind to SOD1 and induce stable and functionally active dimers, which produce excess hydrogen peroxide leading to aberrant cell signalling. Moreover, reactive oxygen species and reactive electrophilic species, simultaneously generated by redox reactions, behave as independent entities that attack a variety of proteins. It is postulated that the binding of the electrophilic moiety to multiple proteins leading to impairing different cellular functions may explain unpredictable side effects in patients undergoing chemotherapy with reactive oxygen species (ROS)-inducing drugs. The identification of proteins susceptible to electrophiles at early steps of oxidative and electrophilic stress is a promising way to offer rational strategies for dealing with stress-related malignant tumors. View Full-Text
Keywords: cancer; electrophilic stress; oxidative stress; reactive molecules; high-throughput screening; microarrays; nitro-benzoxadiazole; fluorescence detection cancer; electrophilic stress; oxidative stress; reactive molecules; high-throughput screening; microarrays; nitro-benzoxadiazole; fluorescence detection
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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. (CC BY 4.0).
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Sakanyan, V. Reactive Chemicals and Electrophilic Stress in Cancer: A Minireview. High-Throughput 2018, 7, 12.

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