NADPH Oxidases: A Perspective on Reactive Oxygen Species Production in Tumor Biology

Abstract

Significance: Reactive oxygen species (ROS) promote genomic instability, altered signal transduction, and an environment that can sustain tumor formation and growth. The NOX family of NADPH oxidases, membranebound epithelial superoxide and hydrogen peroxide producers, plays a critical role in the maintenance of immune function, cell growth, and apoptosis. The impact of NOX enzymes in carcinogenesis is currently being defined and may directly link chronic inflammation and NOX ROS-mediated tumor formation. Recent Advances: Increased interest in the function of NOX enzymes in tumor biology has spurred a surge of investigative effort to understand the variability of NOX expression levels in tumors and the effect of NOX activity on tumor cell proliferation. These initial efforts have demonstrated a wide variance in NOX distribution and expression levels across numerous cancers as well as in common tumor cell lines, suggesting that much remains to be discovered about the unique role of NOX-related ROS production within each system. Progression from in vitro cell line studies toward in vivo tumor tissue screening and xenograft models has begun to provide evidence supporting the importance of NOX expression in carcinogenesis. Critical Issues: A lack of universally available, isoform-specific antibodies and animal tumor models of inducible knockout or over-expression of NOX isoforms has hindered progress toward the completion of in vivo studies. Future Directions: In vivo validation experiments and the use of large, existing gene expression data sets should help define the best model systems for studying the NOX homologues in the context of cancer. Antioxid. Redox Signal. 20, 2873Signal. 20, -2889

Matrix metalloproteinases and gastrointestinal cancers: Impacts of dietary antioxidants

“…- [111] . Increased ROS generation can induce lipid peroxidation and protein oxidation, hampering normal cellular processes.…”

“…ROS also stimulate the expression of Snail and cause damage to DNA and subsequent genomic instability [128] . Reports have suggested a possible association of Nox and Nox-mediated ROS generation for carcinogenesis [111] . Nox1 is involved in H. pylori-induced gastric cancer and in angiogenic responses for tumour formation [129,130] .…”

“…Nox1 is involved in H. pylori-induced gastric cancer and in angiogenic responses for tumour formation [129,130] . Nox2 is involved in phagocytosis; Nox4 controls cell survival in different cancers, including gastric, colon and pancreatic cancers [111,131] . Increased ROS can cause detachment of JNK associated glutathione-S-transferase (GST)-π and thus facilitates JNK activation.…”

Pharmacological Modulation of Proton Channel Hv1 in Cancer Therapy: Future Perspectives

“…Tumor-infiltrating immune cells such as macrophages, neutrophils, dendritic cells, and T cells also display NF-kB activation that facilitates IL-6, IL-1, TNFa, and ROS secretion (Karin and Greten, 2005;Inoue et al, 2007). Correspondingly, NOX isoforms have been detected in several solid tumors Meitzler et al, 2014;Höll et al, 2016) and hematopoietic malignancies (Juhasz et al, 2009;Hole et al, 2013), where they modulate protumoral characteristics that resemble the effects of NF-kB (Maraldi et al, 2009;Meitzler et al, 2014;Sanchez-Sanchez et al, 2014;Liu et al, 2015); in fact, it has been shown that NOX isoform induction is at least partially mediated by NF-kB Roy et al, 2015). Moreover, NOX activity and ROS production in macrophages is required for Treg induction (Kraaij et al, 2010), a key population in controlling T cell responses during inflammatory conditions such as cancer.…”

Avaliação do efeito antiproliferativo da apocinina e diapocinina em células de osteossarcoma humano

“…Diversas pesquisas com osteossarcoma utilizando terapias alternativas foram investigadas (MEYERS et al, 2008;PILZ et al, 2012;SPINA et al, 2013;LUETKE et al, 2014;KUNDU et al, 2014;ANDERSON, 2016 Estudos recentes descreveram o aumento da expressão de Nox1, Nox2, Nox4 e Nox5 em muitas linhagens células de câncer e em tumores humanos no estágio inicial e tardio, indicando sua importância na progressão do câncer (JUHASZ et al, 2010;MEITZLER et al, 2014;HÖLL et al, 2016). Também foi demonstrado que a perda da expressão de Duox1 em células de câncer de pulmão está fortemente associada com a perda do marcador epitelial E-caderina e que o silenciamento do Duox1 promove a transição de célula epitelial para mesenquimal (EMT), uma importante característica do câncer metastático (LITTLE et al, 2016).…”