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Evaluation of the effects of cGMP accumulation in pancreas and lung cancer cells line

Grant number: 13/02246-7
Support Opportunities:Scholarships abroad - Research
Effective date (Start): June 05, 2014
Effective date (End): June 04, 2015
Field of knowledge:Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
Principal Investigator:Fabíola Taufic Monica Iglesias
Grantee:Fabíola Taufic Monica Iglesias
Host Investigator: Ferid Murad
Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Research place: George Washington University, United States  

Abstract

It is well known that nitric oxide (NO) is involved in many physiological processes in the central and peripheral nervous system. However, when NO is produced in lower or higher concentrations it can interfere on many disorders such as auto-imune and degenerative disease, transplant rejection, sepsis, inflammation, cardiovascular disorders and induction or regression of tumors. With respect to tumors, lower concentrations of NO contribute to its development, since NO can increase survival, proliferation, angiogenesis and tumor invasiveness. NO can act by both GMP-dependent and -independent mechanism. The latter is mediated mainly by increased production of oxygen (O2.--, OH.) or nitrogen (NO2., N2O3, ONOO--) reactive species. The NO and other components of the pathway, such as soluble guanylate cyclase (sGC), cGMP-dependent protein protein (PKG) and phosphodiesterases (PDE's) are presented in different types of tumors and can regulate both the survival and apoptosis. Based on the above mentioned some aspects are clearly regarding the role of NO-cGMP-PDE5 in tumors: 1) the expression of alpha-1 and beta-1 subunits of sGC varies among tumors; 2) there exist tumors where PDE5 expression is increased, whereas in others is unaltered; 3) PDE5 inhibitors can have antiproliferative and pro-apoptotic actions; 4) the expression of multi-drug resistant proteins type- 4 (MRP4) and 5 (MRP5) is increased in tumor cells, pumping out AMPc and/c GMPc, respectively and thus contributing for tumor growth. Thus, this project is aimed to evaluate the effect of GMPc accumulation on pulmonary (NCI-H2126 and A549) and pancreatic (PANC-1 e BxPC-3) cancer cells. (AU)

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Scientific publications
(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)
SOTOLONGO, ALEX; MONICA, FABIOLA ZAKIA; KOTS, ALEX; XIAO, HAIJIE; LIU, JUN; SETO, EDWARD; BIAN, KA; MURAD, FERID. Epigenetic regulation of soluble guanylate cyclase (sGC) 1 in breast cancer cells. FASEB JOURNAL, v. 30, n. 9, p. 3171-3180, . (13/02246-7)

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