000058450 001__ 58450
000058450 005__ 20201105083205.0
000058450 0247_ $$2doi$$a10.3389/fphar.2016.00452
000058450 0248_ $$2sideral$$a97441
000058450 037__ $$aART-2016-97441
000058450 041__ $$aeng
000058450 100__ $$aChueca, E.
000058450 245__ $$aProton pump inhibitors display antitumor effects in barrett's adenocarcinoma cells
000058450 260__ $$c2016
000058450 5060_ $$aAccess copy available to the general public$$fUnrestricted
000058450 5203_ $$aRecent evidence has reported that proton pump inhibitors (PPIs) can exert antineoplastic effects through the disruption of pH homeostasis by inhibiting vacuolar ATPase (H+-VATPase), a proton pump overexpressed in several tumor cells, but this aspect has not been deeply investigated in EAC yet. In the present study, the expression of H+-VATPase was assessed through the metaplasia-dysplasia-adenocarcinoma sequence in Barrett''s esophagus (BE) and the antineoplastic effects of PPIs and cellular mechanisms involved were evaluated in vitro. H+-VATPase expression was assessed by immunohistochemistry in paraffined-embedded samples or by immunofluorescence in cultured BE and EAC cell lines. Cells were treated with different concentrations of PPIs and parameters of citotoxicity, oxidative stress, and autophagy were evaluated. H+-VATPase expression was found in all biopsies and cell lines evaluated, showing differences in the location of the pump between the cell lines. Esomeprazole inhibited proliferation and cell invasion and induced apoptosis of EAC cells. Production of reactive oxygen species (ROS) seemed to be involved in the cytotoxic effects observed since the addition of N-acetylcysteine significantly reduced esomeprazole-induced apoptosis in EAC cells. Esomeprazole also reduced intracellular pH of tumor cells, whereas only disturbed the mitochondrial membrane potential in OE33 cells. Esomeprazole induced autophagy in both EAC cells, but also triggered a blockade in autophagic flux in the metastatic cell line. These data provide in vitro evidence supporting the potential use of PPIs as novel antineoplastic drugs for EAC and also shed some light on the mechanisms that trigger PPIs cytotoxic effects, which differ upon the cell line evaluated.
000058450 536__ $$9info:eu-repo/grantAgreement/ES/ISCIII/PI14-01931
000058450 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000058450 590__ $$a4.4$$b2016
000058450 591__ $$aPHARMACOLOGY & PHARMACY$$b33 / 256 = 0.129$$c2016$$dQ1$$eT1
000058450 592__ $$a1.729$$b2016
000058450 593__ $$aPharmacology (medical)$$c2016$$dQ1
000058450 593__ $$aPharmacology$$c2016$$dQ1
000058450 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000058450 700__ $$aApostolova, N.
000058450 700__ $$aEsplugues, J.V.
000058450 700__ $$aGarcía-González, M.A.
000058450 700__ $$0(orcid)0000-0001-5932-2889$$aLanas, Á.$$uUniversidad de Zaragoza
000058450 700__ $$0(orcid)0000-0001-5813-3445$$aPiazuelo, E.$$uUniversidad de Zaragoza
000058450 7102_ $$11005$$2410$$aUniversidad de Zaragoza$$bDpto. Farmacología y Fisiolog.$$cÁrea Fisiología
000058450 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000058450 773__ $$g7, Art 452 (2016), [13 pp.]$$pFront. pharmacol.$$tFrontiers in pharmacology$$x1663-9812
000058450 8564_ $$s3587997$$uhttps://zaguan.unizar.es/record/58450/files/texto_completo.pdf$$yVersión publicada
000058450 8564_ $$s11501$$uhttps://zaguan.unizar.es/record/58450/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000058450 909CO $$ooai:zaguan.unizar.es:58450$$particulos$$pdriver
000058450 951__ $$a2020-11-05-08:18:14
000058450 980__ $$aARTICLE