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NADPH Oxidase Biology and the Regulation of Tyrosine Kinase Receptor Signaling and Cancer Drug Cytotoxicity
Clinical Research Coordination, Nacional Institute of Cancer (INCA), André Cavalcanti Street, 37, Rio de Janeiro, RJ 20231-050, Brazil
Institute of Medical Biochemistry, Federal University of Rio de Janeiro (UFRJ), CCS, Bloco H, University City, Fundão Island, Rio de Janeiro, RJ 21941-590, Brazil
Institute of National Science and Technology of Structural Biology and Bioimage (INCTBEB), CCS, Bloco H, University City, Fundão Island, Rio de Janeiro, RJ 21941-590, Brazil
These authors contributed equally to this work.
* Authors to whom correspondence should be addressed.
Received: 24 December 2012; in revised form: 28 January 2013 / Accepted: 31 January 2013 / Published: 7 February 2013
Abstract: The outdated idea that reactive oxygen species (ROS) are only dangerous products of cellular metabolism, causing toxic and mutagenic effects on cellular components, is being replaced by the view that ROS have several important functions in cell signaling. In aerobic organisms, ROS can be generated from different sources, including the mitochondrial electron transport chain, xanthine oxidase, myeloperoxidase, and lipoxygenase, but the only enzyme family that produces ROS as its main product is the NADPH oxidase family (NOX enzymes). These transfer electrons from NADPH (converting it to NADP−) to oxygen to make O2•−. Due to their stability, the products of NADPH oxidase, hydrogen peroxide, and superoxide are considered the most favorable ROS to act as signaling molecules. Transcription factors that regulate gene expression involved in carcinogenesis are modulated by NADPH oxidase, and it has emerged as a promising target for cancer therapies. The present review discusses the mechanisms by which NADPH oxidase regulates signal transduction pathways in view of tyrosine kinase receptors, which are pivotal to regulating the hallmarks of cancer, and how ROS mediate the cytotoxicity of several cancer drugs employed in clinical practice.
Keywords: NADPH oxidase; reactive oxygen species; cancer; tyrosine kinase receptors; cancer drugs
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Paletta-Silva, R.; Rocco-Machado, N.; Meyer-Fernandes, J.R. NADPH Oxidase Biology and the Regulation of Tyrosine Kinase Receptor Signaling and Cancer Drug Cytotoxicity. Int. J. Mol. Sci. 2013, 14, 3683-3704.
Paletta-Silva R, Rocco-Machado N, Meyer-Fernandes JR. NADPH Oxidase Biology and the Regulation of Tyrosine Kinase Receptor Signaling and Cancer Drug Cytotoxicity. International Journal of Molecular Sciences. 2013; 14(2):3683-3704.
Paletta-Silva, Rafael; Rocco-Machado, Nathália; Meyer-Fernandes, José R. 2013. "NADPH Oxidase Biology and the Regulation of Tyrosine Kinase Receptor Signaling and Cancer Drug Cytotoxicity." Int. J. Mol. Sci. 14, no. 2: 3683-3704.