DR5 Up-Regulation Induced by Dichloroacetate Sensitizes Tumor Cells to Lipid Nanoparticles Decorated with TRAIL

Marco-Brualla, Joaquín (Universidad de Zaragoza) ; de Miguel, Diego ; Martínez-Lostao, Luis (Universidad de Zaragoza) ; Anel, Alberto (Universidad de Zaragoza)

Resumen: 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.

Idioma: Inglés

DOI: 10.3390/jcm12020608

Año: 2023

Publicado en: Journal of Clinical Medicine 12, 2 (2023), 608 [15 pp.]
ISSN: 2077-0383

Factor impacto JCR: 3.0 (2023)

Categ. JCR: MEDICINE, GENERAL & INTERNAL rank: 59 / 329 = 0.179 (2023) - Q1 - T1

Factor impacto CITESCORE: 5.7 - Medicine (all) (Q1)

Factor impacto SCIMAGO: 0.882 - Medicine (miscellaneous) (Q1)

Financiación: info:eu-repo/grantAgreement/ES/DGA/B31-20R
Financiación: info:eu-repo/grantAgreement/ES/MICINN-AEI/PID2019-105128RB-I00/AEI/10.13039/501100011033
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PID2019-105128RB-I00

Tipo y forma: Article (Published version)

Área (Departamento): Área Inmunología (Dpto. Microb.Ped.Radio.Sal.Pú.)
Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)