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

Author(s)

Monteiro, Hugo P. ^[1] ; Rodrigues, Elaine G. ^[2] ; Amorim Reis, Adriana K. C. ^[3] ; Longo, Jr., Luiz S. ^[4] ; Ogata, Fernando T. ^[1] ; Moretti, Ana I. S. ^[5] ; da Costa, Paulo E. ^[1] ; Teodoro, Ana C. S. ^[1] ; Toledo, Mayte S. ^[1] ; Stern, Arnold ^[6]

Affiliation

^[1] Univ Fed Sao Paulo Campus Sao Paulo, Escola Paulista Med, Ctr Cellular & Mol Therapy CTCMol, Dept Biochem, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo Campus Sao Paulo, Escola Paulista Med, Dept Microbiol Immunol & Parasitol, Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo Campus Diadema, Inst Environm Chem & Pharmaceut Sci, Dept Chem, Diadema - Brazil

^[4] Univ Fed Sao Paulo Campus Diadema, Inst Environm Chem & Pharmaceut Sci, Dept Pharmaceut Sci, Diadema - Brazil

^[5] Univ Sao Paulo, Fac Med, Heart Inst, Lab Vasc Biol, Sao Paulo - Brazil

^[6] NYU, Sch Med, New York, NY - USA

• Document type: Journal article
• Source: NITRIC OXIDE-BIOLOGY AND CHEMISTRY; v. 89, p. 1-13, AUG 1 2019.
• Web of Science Citations: 5

Abstract

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. (AU)

• FAPESP's process: 16/06539-7 - INFLAMMATORY AND NITROSATIVE STRESS EVALUATION DURING TUMOR DEVELOPMENT IN HYPERGLICEMIC ENVIRONMENT
• Grantee: Elaine Guadelupe Rodrigues
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/16644-4 - S-nitrosothiols from Aryl-amide and Aryl-pyrimidin-2-ones (thiones) derivatives - potential double inhibitors of HIV-1-PR and renin: synthesis, structural analysis and biological tests
• Grantee: Adriana Karla Cardoso Amorim Reis
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/10470-1 - A role for nitric oxide and for the inducible isoform of nitric oxide synthase in human colon cancer progression
• Grantee: Hugo Pequeno Monteiro
• Support Opportunities: Regular Research Grants