131585 20260217205452.0 doi 10.1038/s41419-024-06492-1 sideral 136959 ART-2024-136959 eng Bayona, Clara (orcid)0000-0001-6786-2041 Tetralol derivative NNC-55-0396 targets hypoxic cells in the glioblastoma microenvironment: an organ-on-chip approach 2024 Access copy available to the general public Unrestricted Glioblastoma (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. info:eu-repo/grantAgreement/EC/H2020/829010/EU/Advanced and versatile PRInting platform for the next generation of active Microfluidic dEvices/PRIME This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 829010-PRIME info:eu-repo/grantAgreement/ES/MINECO/DIN2020-011544 info:eu-repo/grantAgreement/ES/MINECO/RTI2018-094739-B-I00 info:eu-repo/semantics/openAccess by https://creativecommons.org/licenses/by/4.0/deed.es 9.6 2024 CELL BIOLOGY 29 / 204 = 0.142 2024 Q1 T1 2.773 2024 Cancer Research 2024 Q1 Cell Biology 2024 Q1 Medicine (miscellaneous) 2024 Q1 Immunology 2024 Q1 Cellular and Molecular Neuroscience 2024 Q1 15.4 2024 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Alza, Lía Randelovic, Teodora (orcid)0000-0001-7232-7588 Sallán, Marta C. Visa, Anna Cantí, Carles Ochoa, Ignacio Universidad de Zaragoza (orcid)0000-0003-2410-5678 Oliván, Sara Universidad de Zaragoza (orcid)0000-0003-0156-4230 Herreros, Judit 1003 443 Universidad de Zaragoza Dpto. Anatom.Histolog.Humanas Area Histología 15, 2 (2024), 127 [8 pp.] Cell death dis. CELL DEATH & DISEASE 2041-4889 6206384 http://zaguan.unizar.es/record/131585/files/texto_completo.pdf Versión publicada 2952374 http://zaguan.unizar.es/record/131585/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:131585 articulos driver 2026-02-17-20:19:20 ARTICLE