Tetralol derivative NNC-55-0396 targets hypoxic cells in the glioblastoma microenvironment: an organ-on-chip approach

• DOI: 10.1038/s41419-024-06492-1
• Publication Date: 2024-02-10T09:02:27Z
• Authors: Clara Bayona; Lía Alza; Teodora Ranđelović; Marta C. Sallán; Anna Visa; Carles Cantí; Ignacio Ochoa; Sara Oliván; Judit Herreros
• Keywords: Hypoxia

Abstract Glioblastoma (GBM) is a highly malignant brain tumour characterised by limited treatment options and poor prognosis. The microenvironment, particularly the central hypoxic region of tumour, known to play pivotal role in GBM progression. Cells within this adapt hypoxia stabilising transcription factor HIF1-α, which promotes cell proliferation, dedifferentiation chemoresistance. In study we sought examine effects NNC-55-0396, tetralol compound overactivates unfolded protein response inducing apoptosis, using organ-on-chip technology. We identified an increased sensitivity core chip NNC, correlates with decreasing levels HIF1-α vitro. Moreover, NNC blocks macroautophagic process that unleashed as revealed autophagosomal constituent LC3-II autophagy chaperone p62/SQSTM1. specific microenvironment unveil additional anti-cancer abilities further support investigations on its use combined therapies against GBM.