A role for nitric oxide and for the inducible isoform of nitric oxide synthase in human colon cancer progression

• Grant number: 12/10470-1
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2013
• End date: July 31, 2015
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Hugo Pequeno Monteiro
• Grantee: Hugo Pequeno Monteiro
• Host Institution: Centro de Terapia Celular e Molecular. Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Nitric oxide (NO) is a free radical generated from the oxidation of L-arginine in a process catalyzed by the enzymes nitric oxide synthases (NOS). Three NOS isoforms are known: nNOS (neuronal), eNOS (endothelial) and iNOS (inducible). NO* can stimulate cell proliferation or cell death according to cell type and local free radical concentration. NOS isoforms are found in different tumor cell types. However, accumulating experimental evidence demonstrates that iNOS is predominantly expressed in human colon cancer. iNOS epression levels and associated NO production in the tumor microenvironment may result in pro-tumor or anti-tumor activities. For instance, elevated levels of NO produced by iNOS stimulated by inflammatory cytokines in macrophages, often results in cytostatic and/or cytotoxic effects on tumor cells. On the other hand, low concentrations of NO produced by constitutively express iNOS in tumor cells may constitute an important factor for their progression.A number of studies indicate that the importance of NO in tumor progression is associated with s-nitrosylation of Cysteine residues of signaling proteins. Furthermore, this is a research area which is currently under intensive investigation (Batista et al., 2012; Switzer et al., 2012; Wang, 2012). Therefore, the aim of the present study is to establish a role for iNOS and NO in the mediation/modulation of signaling pathways associated with survival, proliferation, and migration of SW480 (primary tumor) and SW620 (metastasis) human colon cancer cell lines. For this purpose we will use human colon cancer cell lines and interference RNA (siRNA) tools. (AU)

Scientific publications

(9)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CARDOSO AMORIM REIS, ADRIANA KARLA; STERN, ARNOLD; MONTEIRO, HUGO PEQUENO. S-nitrosothiols and H2S donors: Potential chemo-therapeutic agents in cancer. REDOX BIOLOGY, v. 27, n. SI, OCT 2019. (16/06539-7, 12/10470-1)

ELLER-BORGES, ROBERTA; RODRIGUES, ELAINE G.; TEODORO, ANA CAROLINE S.; MORAES, MIRIAM S.; ARRUDA, DENISE C.; PASCHOALIN, THAYSA; CURCIO, MARLI F.; COSTA, PAULO E. DA; NASCIMENTO, IGOR R. DO; CALIXTO, LEANDRO A.; et al. Bradykinin promotes murine melanoma cell migration and invasion through endogenous production of superoxide and nitric oxide. NITRIC OXIDE-BIOLOGY AND CHEMISTRY, v. 132, p. 12-pg., 2023-02-03. (17/04592-0, 18/15038-7, 12/10470-1)

CASTRO, ELOISA D.; MATHIAS, PEDRO PAULO M.; BATISTA, WAGNER L.; SATO, ALEX YURI S.; TOLEDO, MAYTE S.; ALMEIDA, VICTOR T.; CURCIO, MARLI F.; COSTA, PAULO E.; STERN, ARNOLD; MONTEIRO, HUGO P.. Knockdown of the inducible nitric oxide synthase (NOS2) splicing variant S3 promotes autophagic cell death from nitrosative stress in SW480 human colon cancer cells. Cell Biology International, v. 46, n. 1, NOV 2021. (18/15038-7, 12/10470-1)

MONTEIRO, HUGO P.; COSTA, PAULO E.; REIS, ADRIANA K. C. A.; STERN, ARNOLD. Nitric oxide: Protein tyrosine phosphorylation and protein S-nitrosylation in cancer. BIOMEDICAL JOURNAL, v. 38, n. 5, p. 380-388, SEP-OCT 2015. (10/19013-7, 13/16644-4, 12/10470-1)

MONTEIRO, HUGO P.; RODRIGUES, ELAINE G.; AMORIM REIS, ADRIANA K. C.; LONGO, JR., LUIZ S.; OGATA, FERNANDO T.; MORETTI, ANA I. S.; DA COSTA, PAULO E.; TEODORO, ANA C. S.; TOLEDO, MAYTE S.; STERN, ARNOLD. Nitric oxide and interactions with reactive oxygen species in the development of melanoma, breast, and colon cancer: A redox signaling perspective. NITRIC OXIDE-BIOLOGY AND CHEMISTRY, v. 89, p. 1-13, AUG 1 2019. (16/06539-7, 13/16644-4, 12/10470-1)

MORAES, MIRIAM S.; COSTA, PAULO E.; BATISTA, WAGNER L.; PASCHOALIN, TAYSA; CURCIO, MARLI F.; BORGES, ROBERTA E.; TAHA, MURCHED O.; FONSECA, FABIO V.; STERN, ARNOLD; MONTEIRO, HUGO P.. Endothelium-derived nitric oxide (NO) activates the NO-epidermal growth factor receptor-mediated signaling pathway in bradykinin-stimulated angiogenesis. Archives of Biochemistry and Biophysics, v. 558, p. 14-27, SEP 15 2014. (10/19013-7, 12/10470-1)

MONTEIRO, HUGO P.; OGATA, FERNANDO T.; STERN, ARNOLD. Thioredoxin promotes survival signaling events under nitrosative/oxidative stress associated with cancer development. BIOMEDICAL JOURNAL, v. 40, n. 4, p. 189-199, AUG 2017. (12/10470-1)

OGATA, FERNANDO TOSHIO; BATISTA, WAGNER LUIZ; SARTORI, ADRIANO; GESTEIRA, TARSIS FERREIRA; MASUTANI, HIROSHI; ARAI, ROBERTO JUN; YODOI, JUNJI; STERN, ARNOLD; MONTEIRO, HUGO PEQUENO. Nitrosative/Oxidative Stress Conditions Regulate Thioredoxin-Interacting Protein (TXNIP) Expression and Thioredoxin-1 (TRX-1) Nuclear Localization. PLoS One, v. 8, n. 12, DEC 20 2013. (12/10470-1)

CARDOSO AMORIM REIS, ADRIANA KARLA; STERN, ARNOLD; MONTEIRO, HUGO PEQUENO. S-nitrosothiols and H2S donors: Potential chemo-therapeutic agents in cancer. REDOX BIOLOGY, v. 27, p. 8-pg., 2019-10-01. (12/10470-1, 16/06539-7)