Inducible Nitric Oxide Synthase in the Carcinogenesis of Gastrointestinal Cancers

Oliveira, Gustavo H. C.; Cheng, Robert; Ridnour, Lisa A.; Basudhar, Debashree; Somasundaram, Veena; McVicar, Daniel W.; Monteiro, Hugo P.; Wink, David A.

doi:10.1089/ars.2016.6850

Cited by 67 publications

(57 citation statements)

References 185 publications

(179 reference statements)

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“…Although, the role NO plays in tumors is difficult to predict, the evidence suggests that it depends on the organ of primary tumor [6, 14], stage of disease progression [7, 8] and the types of cancer-associated stromal cells within the TME [16, 20]. Sufficient interest has been generated in developing anticancer drugs that target NO metabolism, but progress towards clinical applications of NOS inhibitors or NO-donors has been limited.…”

Section: Discussionmentioning

confidence: 99%

“…Increase in exogenous NO in the TME is also associated with tumorigenic functions in colon cancer patients. Colon cancer patients with high NOS2 expression have increased incidences of lymph node metastasis; and elevated NOS2 expression observed in the upper colon in colitis patients indicates higher risk of developing colon cancer [7, 8]. In addition to regulating metastasis and tumor initiation, NO is also a key regulator of angiogenesis .…”

Section: No: Modulator Of the Tmementioning

confidence: 99%

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Nitric Oxide: The Forgotten Child of Tumor Metabolism

2017

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Nitric oxide (NO) is a signaling molecule with pleiotropic physiological roles in normal cells and pathophysiological roles in cancer. NO synthetase expression and NO synthesis are linked to altered metabolism, neoplasticity, invasiveness, chemoresistance, immune evasion, and ultimately to poor prognosis of cancer patients. Exogenous NO in the microenvironment facilitates paracrine signaling, mediates immune responses, and triggers angiogenesis. NO regulates posttranslational protein modifications, S-nitrosation, and genome-wide epigenetic modifications that can have both tumor-promoting and tumor-suppressing effects. We review mechanisms that link NO to cancer hallmarks, with a perspective of co-targeting NO metabolism with first-line therapies for improved outcome. We highlight the need for quantitative flux analysis to study NO in tumors.

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Section: Discussionmentioning

confidence: 99%

Section: No: Modulator Of the Tmementioning

confidence: 99%

Nitric Oxide: The Forgotten Child of Tumor Metabolism

2017

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“…These include colon, breast, gastric, hepatocellular carcinoma, melanoma, ovarian, leukemia, gastric, prostate, esophageal, and cervical [279, 280]. It has thus been suggested that iNOS expression may be used as a biomarker of poor patient prognosis and perhaps survival [281, 282]. By contrast, favorable prognosis has been associated with high iNOS expression in ovarian (10-year prognosis) [283] and non-small cell lung cancers [284].…”

Section: Modulation Of No Levels As a Strategy To Treat Cancermentioning

confidence: 99%

The dichotomous role of H2S in cancer cell biology? Déjà vu all over again

Kashfi

2018

Biochemical Pharmacology

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Nitric oxide (NO) a gaseous free radical is one of the ten smallest molecules found in nature, while hydrogen sulfide (HS) is a gas that bears the pungent smell of rotten eggs. Both are toxic yet they are gasotransmitters of physiological relevance. There appears to be an uncanny resemblance between the general actions of these two gasotransmitters in health and disease. The role of NO and HS in cancer has been quite perplexing, as both tumor promotion and inflammatory activities as well as anti-tumor and antiinflammatory properties have been described. These paradoxes have been explained for both gasotransmitters in terms of each having a dual or biphasic effect that is dependent on the local flux of each gas. In this review/commentary, I have discussed the major roles of NO and HS in carcinogenesis, evaluating their dual nature, focusing on the enzymes that contribute to this paradox and evaluate the pros and cons of inhibiting or inducing each of these enzymes.

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“…The maintenance of cell redox state is important to cell viability [43]. The increased level of reactive species can lead to oxidative damage to a vast number of biological molecules, as DNA [44][45][46], proteins [47], lipids [48], including membranes [3] leading to a range of pathologies, as cancer [36], neurological disease [49], cardiac disease [50,51], inflammation process [52] and aging.…”

Section: Cellular Respiration and Generation Of Reactive Species In Tmentioning

confidence: 99%

“…Nitric oxide is a membrane permeable free radical that participates in a multiple process in the cells as signaling molecule, but also can contribute in cell oxidative damage. Its effect depends on NO levels and localization in the cell microenvironment [35,36]. When nitric oxide is present in environment, as in mitochondrial matrix, the reaction of this free radical with superoxide can form others RNS, as peroxynitrite.…”

mentioning

confidence: 99%

Oxidative Stress: Noxious but Also Vital

Bagatini¹,

Jaques²,

Oliveira³

et al. 2018

Novel Prospects in Oxidative and Nitrosative Stress

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The imbalance between reactive oxygen species (ROS) production and antioxidant defenses determines the condition called oxidative stress. When there is an increase in ROS production or a decrease in the antioxidant defenses, this systemic antioxidant/pro-oxidant imbalance may lead to the accumulation of oxidative damage, which, in turn, may lead to a modification of biomolecules. These consist of reactions resulting in protein adducts, DNA oxidation, and formation of lipid peroxides, which, in turn, reduce the cellular functional capacity and increase the risk of disease development. The body has natural scavenging systems against free radicals and other reactive species. However, sometimes the endogenous antioxidant capacity is exceeded by the production of ROS. When this occurs, exogenous antioxidants exert important function for the human health. These bioactive compounds act preventing and neutralizing the formation of new reactive species and free radical s .I ns o m ec a s e s ,a n increase of ROS can help the host to resolve an infection or even to control the tumor growth. Finally, the levels of ROS can be perceived by signal transduction pathways involving known targets(i.e.,p53,Ras,andNF-κB) and regulate physiopathological events such as the cellular cycle, apoptosis, and inflammation.Keywords: reactive species, cellular oxidation, antioxidant system, health, disease © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Cellular respiration and generation of reactive species in the mitochondria: implications in cell viability and agingOxidative phosphorylation is the center of energy metabolism in plants, animals and several microbial life forms [1]. In eukaryotes, this process occurs in mitochondria. The mitochondria is a cytoplasmic organelle surrounded by two membranes, outer and inner membrane, which main function is the production of most of the phosphate compounds necessary for the energetic balance of the cell. In addition, other functions such as the regulation of the body'sheatgeneration [2][3][4] programmed cell death [5][6][7], reactive oxygen species (ROS) generation and cell signaling [8] is also associated with mitochondria. Cellular vitality is directly related to mitochondria, and mitochondrial dysfunctions are frequent causes of accidental cell death [5,[9][10][11], cancer [12, 13], diabetes [14][15][16] and neurodegenerative diseases [17][18][19], among others.The characterization of the respiratory electron chain could be performed in studies using the fractionation of its components by certain detergents that at low concentrations break the interactions between proteins and lipids in the membranes, leaving associations between proteins intact [20]. In electron transport chain, through this process, four protein complexes were found....

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Inducible Nitric Oxide Synthase in the Carcinogenesis of Gastrointestinal Cancers

Abstract: Understanding the underlying mechanism involved in NOS2 activation can provide new insights into important prevention and treatment strategies. Antioxid. Redox Signal. 26, 1059-1077.

Cited by 67 publications

References 185 publications

Nitric Oxide: The Forgotten Child of Tumor Metabolism

Nitric Oxide: The Forgotten Child of Tumor Metabolism

The dichotomous role of H2S in cancer cell biology? Déjà vu all over again

Oxidative Stress: Noxious but Also Vital

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