121869 20241125101128.0 doi 10.3390/jcm12020608 sideral 132219 ART-2023-132219 eng Marco-Brualla, Joaquín Universidad de Zaragoza DR5 Up-Regulation Induced by Dichloroacetate Sensitizes Tumor Cells to Lipid Nanoparticles Decorated with TRAIL 2023 Access copy available to the general public Unrestricted Cancer 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. info:eu-repo/grantAgreement/ES/DGA/B31-20R info:eu-repo/grantAgreement/ES/MICINN-AEI/PID2019-105128RB-I00/AEI/10.13039/501100011033 info:eu-repo/grantAgreement/ES/MICINN/PID2019-105128RB-I00 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 3.0 2023 MEDICINE, GENERAL & INTERNAL 59 / 329 = 0.179 2023 Q1 T1 0.882 2023 Medicine (miscellaneous) 2023 Q1 5.7 2023 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion de Miguel, Diego Martínez-Lostao, Luis Universidad de Zaragoza (orcid)0000-0003-3043-147X Anel, Alberto Universidad de Zaragoza (orcid)0000-0002-5175-8394 1011 566 Universidad de Zaragoza Dpto. Microb.Ped.Radio.Sal.Pú. Área Inmunología 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 12, 2 (2023), 608 [15 pp.] J. clin.med. Journal of Clinical Medicine 2077-0383 3349632 http://zaguan.unizar.es/record/121869/files/texto_completo.pdf Versión publicada 2748371 http://zaguan.unizar.es/record/121869/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:121869 articulos driver 2024-11-22-11:58:11 ARTICLE