000131585 001__ 131585
000131585 005__ 20240529142852.0
000131585 0247_ $$2doi$$a10.1038/s41419-024-06492-1
000131585 0248_ $$2sideral$$a136959
000131585 037__ $$aART-2024-136959
000131585 041__ $$aeng
000131585 100__ $$0(orcid)0000-0001-6786-2041$$aBayona, Clara
000131585 245__ $$aTetralol derivative NNC-55-0396 targets hypoxic cells in the glioblastoma microenvironment: an organ-on-chip approach
000131585 260__ $$c2024
000131585 5060_ $$aAccess copy available to the general public$$fUnrestricted
000131585 5203_ $$aGlioblastoma (GBM) is a highly malignant brain tumour characterised by limited treatment options and poor prognosis. The tumour microenvironment, particularly the central hypoxic region of the tumour, is known to play a pivotal role in GBM progression. Cells within this region adapt to hypoxia by stabilising transcription factor HIF1-α, which promotes cell proliferation, dedifferentiation and chemoresistance. In this study we sought to examine the effects of NNC-55-0396, a tetralol compound which overactivates the unfolded protein response inducing apoptosis, using the organ-on-chip technology. We identified an increased sensitivity of the hypoxic core of the chip to NNC, which correlates with decreasing levels of HIF1-α in vitro. Moreover, NNC blocks the macroautophagic process that is unleashed by hypoxia as revealed by increased levels of autophagosomal constituent LC3-II and autophagy chaperone p62/SQSTM1. The specific effects of NNC in the hypoxic microenvironment unveil additional anti-cancer abilities of this compound and further support investigations on its use in combined therapies against GBM.
000131585 536__ $$9info:eu-repo/grantAgreement/EC/H2020/829010/EU/Advanced and versatile PRInting platform for the next generation of active Microfluidic dEvices/PRIME$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 829010-PRIME$$9info:eu-repo/grantAgreement/ES/MINECO/DIN2020-011544$$9info:eu-repo/grantAgreement/ES/MINECO/RTI2018-094739-B-I00
000131585 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000131585 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000131585 700__ $$aAlza, Lía
000131585 700__ $$0(orcid)0000-0001-7232-7588$$aRandelovic, Teodora
000131585 700__ $$aSallán, Marta C.
000131585 700__ $$aVisa, Anna
000131585 700__ $$aCantí, Carles
000131585 700__ $$0(orcid)0000-0003-2410-5678$$aOchoa, Ignacio$$uUniversidad de Zaragoza
000131585 700__ $$0(orcid)0000-0003-0156-4230$$aOliván, Sara$$uUniversidad de Zaragoza
000131585 700__ $$aHerreros, Judit
000131585 7102_ $$11003$$2443$$aUniversidad de Zaragoza$$bDpto. Anatom.Histolog.Humanas$$cArea Histología
000131585 773__ $$g15, 2 (2024), 127 [8 pp.]$$pCell death dis.$$tCELL DEATH & DISEASE$$x2041-4889
000131585 8564_ $$s6206384$$uhttps://zaguan.unizar.es/record/131585/files/texto_completo.pdf$$yVersión publicada
000131585 8564_ $$s2952374$$uhttps://zaguan.unizar.es/record/131585/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000131585 909CO $$ooai:zaguan.unizar.es:131585$$particulos$$pdriver
000131585 951__ $$a2024-05-29-14:25:42
000131585 980__ $$aARTICLE