000120915 001__ 120915
000120915 005__ 20241125101124.0
000120915 0247_ $$2doi$$a10.1007/s13105-022-00931-3
000120915 0248_ $$2sideral$$a131269
000120915 037__ $$aART-2023-131269
000120915 041__ $$aeng
000120915 100__ $$0(orcid)0000-0002-5306-9365$$aGrasa, Laura$$uUniversidad de Zaragoza
000120915 245__ $$aAntitumor effects of lactate transport inhibition on esophageal adenocarcinoma cells
000120915 260__ $$c2023
000120915 5060_ $$aAccess copy available to the general public$$fUnrestricted
000120915 5203_ $$aAs a consequence of altered glucose metabolism, cancer cell intake is increased, producing large amounts of lactate which is pumped out the cytosol by monocarboxylate transporters (MCTs). MCT 1 and MCT4 are frequently overexpressed in tumors, and recently, MCT inhibition has been reported to exert antineoplastic effects. In the present study, MCT1 and MCT4 levels were assessed in esophageal adenocarcinoma (EAC) cells and the effects of the MCT-1 selective inhibitor AZD3965, hypoxia, and a glucose overload were evaluated in vitro. Two EAC cell lines (OE33 and OACM5.1C) were treated with AZD3965 (10–100 nM) under different conditions (normoxia/hypoxia) and also different glucose concentrations, and parameters of cytotoxicity, oxidative stress, intracellular pH (pHi), and lactate levels were evaluated. MCT1 was present in both cell lines whereas MCT4 was expressed in OE33 cells and only in a small proportion of OACM5.1C cells. Glucose addition did not have any effect on apoptosis nor cell proliferation. AZD3965 increased apoptosis and reduced proliferation of OACM5.1C cells, effects which were abrogated when cells were growing in hypoxia. MCT1 inhibition increased intracellular lactate levels in all the cells evaluated, but this increase was higher in cells expressing only MCT1 and did not affect oxidative stress. AZD3965 induced a decrease in pHi of cells displaying low levels of MCT4 and also increased the sodium/hydrogen exchanger 1 (NHE-1) expression on these cells. These data provide in vitro evidence supporting the potential of MCT inhibitors as novel antineoplastic drugs for EAC and highlight the importance of achieving a complete MCT inhibition.
000120915 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B25-17R$$9info:eu-repo/grantAgreement/ES/ISCIII/PI14-01931
000120915 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000120915 590__ $$a3.7$$b2023
000120915 592__ $$a0.953$$b2023
000120915 591__ $$aPHYSIOLOGY$$b17 / 85 = 0.2$$c2023$$dQ1$$eT1
000120915 593__ $$aMedicine (miscellaneous)$$c2023$$dQ1
000120915 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b119 / 313 = 0.38$$c2023$$dQ2$$eT2
000120915 593__ $$aPhysiology$$c2023$$dQ2
000120915 593__ $$aBiochemistry$$c2023$$dQ2
000120915 594__ $$a6.6$$b2023
000120915 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000120915 700__ $$aChueca, Eduardo
000120915 700__ $$aArechavaleta, Samantha
000120915 700__ $$aGarcía-González, María Asunción
000120915 700__ $$0(orcid)0000-0001-5724-3853$$aSáenz, María Ángeles$$uUniversidad de Zaragoza
000120915 700__ $$aValero, Alberto
000120915 700__ $$aHördnler, Carlos
000120915 700__ $$0(orcid)0000-0001-5932-2889$$aLanas, Ángel$$uUniversidad de Zaragoza
000120915 700__ $$0(orcid)0000-0001-5813-3445$$aPiazuelo, Elena$$uUniversidad de Zaragoza
000120915 7102_ $$11012$$2410$$aUniversidad de Zaragoza$$bDpto. Farmac.Fisiol.y Med.L.F.$$cÁrea Fisiología
000120915 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000120915 7102_ $$11012$$2315$$aUniversidad de Zaragoza$$bDpto. Farmac.Fisiol.y Med.L.F.$$cÁrea Farmacología
000120915 773__ $$g79, 1 (2023), 147–161$$pJ. physiol. biochem.$$tJournal of Physiology and Biochemistry$$x1138-7548
000120915 8564_ $$s10813949$$uhttps://zaguan.unizar.es/record/120915/files/texto_completo.pdf$$yVersión publicada
000120915 8564_ $$s2345434$$uhttps://zaguan.unizar.es/record/120915/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000120915 909CO $$ooai:zaguan.unizar.es:120915$$particulos$$pdriver
000120915 951__ $$a2024-11-22-11:57:20
000120915 980__ $$aARTICLE