000121869 001__ 121869
000121869 005__ 20241125101128.0
000121869 0247_ $$2doi$$a10.3390/jcm12020608
000121869 0248_ $$2sideral$$a132219
000121869 037__ $$aART-2023-132219
000121869 041__ $$aeng
000121869 100__ $$aMarco-Brualla, Joaquín$$uUniversidad de Zaragoza
000121869 245__ $$aDR5 Up-Regulation Induced by Dichloroacetate Sensitizes Tumor Cells to Lipid Nanoparticles Decorated with TRAIL
000121869 260__ $$c2023
000121869 5060_ $$aAccess copy available to the general public$$fUnrestricted
000121869 5203_ $$aCancer resistance to treatments is a challenge that researchers constantly seek to overcome. For instance, TNF-related apoptosis-inducing ligand (TRAIL) is a potential good prospect as an anti-cancer therapy, as it attacks tumor cells but not normal cells. However, treatments based in soluble TRAIL provided incomplete clinical results and diverse formulations have been developed to improve its bioactivity. In previous works, we generated a new TRAIL formulation based in its attachment to the surface of unilamellar nanoliposomes (LUV-TRAIL). This formulation greatly increased apoptosis in a wide selection of tumor cell types, albeit a few of them remained resistant. On the other hand, it has been described that a metabolic shift in cancer cells can also alter its sensitivity to other treatments. In this work, we sought to increase the sensitivity of several tumor cell types resistant to LUV-TRAIL by previous exposure to the metabolic drug dichloroacetate (DCA), which forces oxidative phosphorylation. Results showed that DCA + LUV-TRAIL had a synergistic effect on both lung adenocarcinoma A549, colorectal HT29, and breast cancer MCF7 cells. Despite DCA inducing intracellular changes in a cell-type specific way, the increase in cell death by apoptosis was clearly correlated with an increase in death receptor 5 (DR5) surface expression in all cell lines. Therefore, DCA-induced metabolic shift emerges as a suitable option to overcome TRAIL resistance in cancer cells.
000121869 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B31-20R$$9info:eu-repo/grantAgreement/ES/MICINN-AEI/PID2019-105128RB-I00/AEI/10.13039/501100011033$$9info:eu-repo/grantAgreement/ES/MICINN/PID2019-105128RB-I00
000121869 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000121869 590__ $$a3.0$$b2023
000121869 592__ $$a0.882$$b2023
000121869 591__ $$aMEDICINE, GENERAL & INTERNAL$$b59 / 329 = 0.179$$c2023$$dQ1$$eT1
000121869 593__ $$aMedicine (miscellaneous)$$c2023$$dQ1
000121869 594__ $$a5.7$$b2023
000121869 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000121869 700__ $$ade Miguel, Diego
000121869 700__ $$0(orcid)0000-0003-3043-147X$$aMartínez-Lostao, Luis$$uUniversidad de Zaragoza
000121869 700__ $$0(orcid)0000-0002-5175-8394$$aAnel, Alberto$$uUniversidad de Zaragoza
000121869 7102_ $$11011$$2566$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Inmunología
000121869 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000121869 773__ $$g12, 2 (2023), 608 [15 pp.]$$pJ. clin.med.$$tJournal of Clinical Medicine$$x2077-0383
000121869 8564_ $$s3349632$$uhttps://zaguan.unizar.es/record/121869/files/texto_completo.pdf$$yVersión publicada
000121869 8564_ $$s2748371$$uhttps://zaguan.unizar.es/record/121869/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000121869 909CO $$ooai:zaguan.unizar.es:121869$$particulos$$pdriver
000121869 951__ $$a2024-11-22-11:58:11
000121869 980__ $$aARTICLE