NADPH Oxidases: Insights into Selected Functions and Mechanisms of Action in Cancer and Stem Cells

Skonieczna, Magdalena; Hejmo, Tomasz; Poterała-Hejmo, Aleksandra; Cieślar-Pobuda, Artur; Bułdak, Rafał Jakub

doi:10.1155/2017/9420539

Cited by 114 publications

(106 citation statements)

References 152 publications

(182 reference statements)

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“…Generation of extracellular O 2 · through NOX is associated with oncogene activation and seems to be required for the control of cell proliferation and maintenance of the transformed state [25]. This protein consists of among other peptides by a regulatory 22-kDa α-subunit (p22phox) and a 91-kDa catalytic β-subunit (gp91phox).…”

Section: Nad(p)h Oxidase (Nox)mentioning

confidence: 99%

Microenvironment in Vagina as a Key-Player on Cervical Cancer: Interaction of Polymorphic Genetic Variants and Vaginal Microbiome as Co-Factors

Matos¹,

Silva²,

Medeiros³

et al. 2018

Cervical Cancer - Screening, Treatment and Prevention - Universal Protocols for Ultimate Control

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Current knowledge point to persistence of risk factors for the development of cervical intraepithelial neoplasia. The infection with a high-risk oncogenic Human Papillomavirus (HPV) subtypes, most commonly 16 and 18, is a necessary, although not sufficient, condition for development of invasive cervical cancer (ICC) and its precancerous precursor, cervical intra-epithelial neoplasia (CIN). It has been suggested that CIN disease severity and the diversity of vaginal microbiota are associated and this may determine viral persistence and disease behaviour. Our work focuses on the genetic variability associated to the modulation of genotoxicity induced by vaginal microbiota diversity. Relatively little is known about the mechanisms associated with clearance or persistence of HPV infection, therefore we hypothesized that may be under the influence of the genetic background.

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Section: Nad(p)h Oxidase (Nox)mentioning

confidence: 99%

Microenvironment in Vagina as a Key-Player on Cervical Cancer: Interaction of Polymorphic Genetic Variants and Vaginal Microbiome as Co-Factors

Matos¹,

Silva²,

Medeiros³

et al. 2018

Cervical Cancer - Screening, Treatment and Prevention - Universal Protocols for Ultimate Control

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“…AMPK exerts powerful anti-inflammatory effects, including inhibition of NOX-mediated ROS production [139,140], iNOS-mediated NO production [141], and NF-κB-mediated production of proinflammatory cytokines such as IL-1 and TNFα [28,142]. Furthermore, the transition from M2 to M1, involves a critical metabolic switch from OXPHOS to glycolysis.…”

Section: Functions Of Ampk and Their Relevance To Pdmentioning

confidence: 99%

Targeting AMPK Signaling as a Neuroprotective Strategy in Parkinson’s Disease

Curry

Stutz

Andrews

et al. 2018

JPD

112

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Parkinson’s disease (PD) is the second most common neurodegenerative disorder. It is characterized by the accumulation of intracellular α-synuclein aggregates and the degeneration of nigrostriatal dopaminergic neurons. While no treatment strategy has been proven to slow or halt the progression of the disease, there is mounting evidence from preclinical PD models that activation of 5’-AMP-activated protein kinase (AMPK) may have broad neuroprotective effects. Numerous dietary supplements and pharmaceuticals (e.g. metformin) that increase AMPK activity are available for use in humans, but clinical studies of their effects in PD patients are limited. AMPK is an evolutionarily conserved serine/threonine kinase that is activated by falling energy levels and functions to restore cellular energy balance. However, in response to certain cellular stressors, AMPK activation may exacerbate neuronal atrophy and cell death. This review describes the regulation and functions of AMPK, evaluates the controversies in the field, and assesses the potential of targeting AMPK signaling as a neuroprotective treatment for PD.

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“…Furthermore, higher cytosolic NADPH levels will activate the NOX's to overproduce ROS, which are important for growth of cancer and CSCs. 105 However, if NADPH levels are raised excessively, such as by inhibiting fatty acid synthesis, the resulting NOX-mediated ROS production can cause cancer cell apoptosis. 106 From the above data, the evidence is becoming clear that metabolic reprogramming for NADPH production is supported as one means for GSSG to GSH regeneration in the cytosol of metastatic cancer cells and as a mechanism for enhancing cell survival in the presence of the heightened ROS levels found inside metastatic cancer cells.…”

Section: Why the Mitochondrial Ros Production System Provides Novelmentioning

confidence: 99%

“…Interestingly, NRF2 not only upregulates the PPP NADPH‐producing enzymes, Glc6PDH and 6PGDH, but also upregulates NADPH oxidases (NOXs) and the ROS produced by the NOXs can activate more NRF2 (reviewed in Dinkova‐Kostova and Abramov). Furthermore, higher cytosolic NADPH levels will activate the NOX's to overproduce ROS, which are important for growth of cancer and CSCs . However, if NADPH levels are raised excessively, such as by inhibiting fatty acid synthesis, the resulting NOX‐mediated ROS production can cause cancer cell apoptosis …”

Section: Introductionmentioning

confidence: 99%

Repurposing drugs as pro‐oxidant redox modifiers to eliminate cancer stem cells and improve the treatment of advanced stage cancers

Ralph

Nozuhur

ALHulais

et al. 2019

Medicinal Research Reviews

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Over the last decade, three major advances have contributed in improving the response rates against cancer including, immunotherapy; greater understanding of the molecular, biochemical, and cellular mechanisms in carcinogenesis thereby providing drug targets; and identification of reliable biomarkers for early detection to facilitate the earlier stage treatment of disease. However, no single universal cancer cure has yet been found, although combinations from the above areas have steadily improved survival outcomes. Hence, chemotherapy remains a key component in the oncologist's arsenal for cancer therapy, despite frequent development of drug resistance and more aggressive cancers with onset of advanced stage metastases. The focus here is to explore the repurposing of old drugs that cause pro‐oxidative overload to overcome onset of resistance to chemotherapy and enhance chemotherapeutic responses, particularly against metastatic cancer. Excellent examples of US Food and Drug Administration approved drugs suitable for repurposing are the potent and specific thioreductase inhibitor auranofin and the nonsteroidal anti‐inflammatory drug, celecoxib. Recently, both drugs were shown to selectively target and kill metastatic cancer cells and cancer stem cells (CSCs), predominantly by promoting excessive mitochondrial reactive oxygen species. Thus, targeting intracellular redox systems of advanced stage metastatic cancer cells and CSCs can promote an overload of pro‐oxidative stress to activate the intrinsic pathway for programmed cell death. It is envisaged that more clinical studies will incorporate longer term use of repurposed drugs, such as auranofin or celecoxib, to target redox systems in cancer cells as part of common practice postcancer diagnosis, providing enhanced chemotherapeutic responses and increased cancer survival.

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NADPH Oxidases: Insights into Selected Functions and Mechanisms of Action in Cancer and Stem Cells

Cited by 114 publications

References 152 publications

Microenvironment in Vagina as a Key-Player on Cervical Cancer: Interaction of Polymorphic Genetic Variants and Vaginal Microbiome as Co-Factors

Microenvironment in Vagina as a Key-Player on Cervical Cancer: Interaction of Polymorphic Genetic Variants and Vaginal Microbiome as Co-Factors

Targeting AMPK Signaling as a Neuroprotective Strategy in Parkinson’s Disease

Repurposing drugs as pro‐oxidant redox modifiers to eliminate cancer stem cells and improve the treatment of advanced stage cancers

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