Nitric oxide and interactions with reactive oxygen species in the development of melanoma, breast, and colon cancer: A redox signaling perspective

Cancer development is closely related to chronic inflammation, which is associated with identifiable markers of tumor progression, such as uncontrolled cell proliferation, angiogenesis, genomic instability, chemotherapeutic resistance, and metastases. Redox processes mediated by reactive oxygen spec...

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Bibliographic Details
Published in:Nitric oxide 2019-08, Vol.89, p.1-13
Main Authors: Monteiro, Hugo P., Rodrigues, Elaine G., Amorim Reis, Adriana K.C., Longo, Luiz S., Ogata, Fernando T., Moretti, Ana I.S., da Costa, Paulo E., Teodoro, Ana C.S., Toledo, Maytê S., Stern, Arnold
Format: Article
Language:English
Subjects:
Animals
Breast Neoplasms - drug therapy
Breast Neoplasms - physiopathology
Cancer
Cell Line, Tumor
Colonic Neoplasms - drug therapy
Colonic Neoplasms - physiopathology
Epithelial-mesenchymal transition
Epithelial-Mesenchymal Transition - physiology
Humans
Melanoma - drug therapy
Melanoma - physiopathology
Mesenchymal-epithelial transition
Nitric oxide
Nitric Oxide - metabolism
Nitric Oxide Donors - therapeutic use
Reactive oxygen species
Reactive Oxygen Species - metabolism
Redox homeostasis
Redox signaling
Signal Transduction - physiology
Tumor Microenvironment - physiology
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Summary:Cancer development is closely related to chronic inflammation, which is associated with identifiable markers of tumor progression, such as uncontrolled cell proliferation, angiogenesis, genomic instability, chemotherapeutic resistance, and metastases. Redox processes mediated by reactive oxygen species (ROS) and nitric oxide (NO) within the inflammatory tumor microenvironment play an essential role in directly influencing intercellular and intracellular signaling. These reactive species originating in the cancer cell or its microenvironment, mediate the epithelial-mesenchymal transition (EMT) and the mesenchymal-epithelial transition (MET). However, intracellular interactions between NO and ROS must be controlled to prevent cell death. Melanoma, breast, and colon cancer cells have developed a mechanism to survive and adapt to oxidative and nitrosative stress. The mechanism involves a spatial-temporal fine adjustment of the intracellular concentrations of NO and ROS, thereby guaranteeing the successful development of cancer cells. Physiological concentrations of NO and supra physiological concentrations of ROS are prevalent in cancer cells at the primary site. The situation reverses in cancer cells undergoing the EMT prior to being released into the blood stream. Intracellular supra physiological concentrations of NO found in circulating cancer cells endow them with anoikis resistance. When the anoikis-resistant cancer cells arrive at a metastatic site they undergo the MET. Endogenous supra physiological concentrations of ROS and physiological NO concentrations are prevalent in these cells. Understanding tumor progression from the perspective of redox signaling permits the characterization of new markers and approaches to therapy. The synthesis and use of compounds with the capacity of modifying intracellular concentrations of NO and ROS may prove effective in disrupting a redox homeostasis operative in cancer cells. •NO and ROS are potential mediators of the epithelial-mesenchymal (EMT) and mesenchymal-epithelial (MET) transitions in cancer development.•Low concentrations of NO and high concentrations of ROS would be prevalent in primary tumors.•After EMT high concentrations of NO and low concentrations of ROS maintain tumor cell homeostasis. This situation is reversed after MET.•A fine spatiotemporal control of ROS and NO concentrations must be operational for the successful completion of all tumor developmental stages.•Compounds that modify the intracell
ISSN:1089-8603
1089-8611
DOI:10.1016/j.niox.2019.04.009