Role of soluble guanylyl cyclase-cyclic GMP signaling in tumor cell proliferation.

Nitric Oxide : Biology and Chemistry
Kalpana MujooFerid Murad

Abstract

Our previous studies demonstrate a differential expression of nitric oxide (NO) signaling components in ES cells and our recent study demonstrated an enhanced differentiation of ES cells into myocardial cells with NO donors and soluble guanylyl cyclase (sGC) activators. Since NO-cGMP pathway exhibits a diverse role in cancer, we were interested in evaluating the role of the NO-receptor sGC and other components of the pathway in regulation of the tumor cell proliferation. Our results demonstrate a differential expression of the sGC subunits, NOS-1 and PKG mRNA and protein levels in various human cancer models. In contrast to sGC alpha(1), robust levels of sGC beta(1) were observed in OVCAR-3 (ovarian) and MDA-MB-468 (breast) cancer cells which correlated well with the sGC activity and a marked increase in cGMP levels upon exposure to the combination of a NO donor and a sGC activator. NOC-18 (DETA NONOate; NO donor), BAY41-2272 (3-(4-amino-5-cyclopropylpyrimidin-2-yl)-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine); sGC activator), NOC-18+BAY41-2272, IBMX (3-isobutyl-1-methylxanthine; phosphodiesterase inhibitor) and 8-bromo-cGMP (cGMP analog) caused growth inhibition and apoptosis in various cancer cell lines. To elucidate the mo...Continue Reading

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Citations

Dec 16, 2011·The Journal of Pharmacology and Experimental Therapeutics·Iraida SharinaEmil Martin
Apr 13, 2013·Journal of Medical Toxicology : Official Journal of the American College of Medical Toxicology·David H JangRobert S Hoffman
Feb 20, 2016·Nitric Oxide : Biology and Chemistry·Ahmed El-SehemyYangXin Fu
Sep 7, 2011·Trends in Pharmacological Sciences·Christopher H SwitzerDavid A Wink
Mar 28, 2016·Critical Reviews in Oncology/hematology·Veena SomasundaramPriya Srinivas
Jun 21, 2012·IUBMB Life·Ka BianFerid Murad
Aug 26, 2014·Nitric Oxide : Biology and Chemistry·Ka Bian, Ferid Murad
Jul 2, 2014·Biochimica Et Biophysica Acta·Philippe IcardHubert Lincet
Jul 31, 2012·Biochimica Et Biophysica Acta·Philippe Icard, Hubert Lincet
Nov 24, 2012·Breast Cancer Research : BCR·Anna A MourskaiaPeter M Siegel
Mar 23, 2019·Expert Opinion on Pharmacotherapy·Fabiola Zakia Mónica, Gilberto De Nucci
Jun 10, 2016·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Alex SotolongoFerid Murad
Nov 7, 2019·BMC Genomics·Pavel AbaffyRadek Sindelka
Feb 13, 2020·International Journal of Molecular Sciences·Krassimira Ivanova, Ruth Hemmersbach
Apr 26, 2013·Bulletin du cancer·Philippe Icard, Hubert Lincet
Jan 14, 2021·Transplantation Direct·Tara TalaieChristine L Lau
Dec 9, 2020·Journal of Natural Products·Olga N PetrovaMichel Negrerie

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