{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:52:55Z","timestamp":1791175975419,"version":"4.1.0"},"reference-count":52,"publisher":"Spandidos Publications","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomed Rep"],"DOI":"10.3892\/br.2026.2202","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T10:49:16Z","timestamp":1789123756000},"page":"1-12","source":"Crossref","is-referenced-by-count":0,"title":["Nrf2 and PGC\u20111\u03b1 signaling in temozolomide resistance in glioblastoma under hypoxia"],"prefix":"10.3892","volume":"25","author":[{"given":"Pinpat","family":"Tripatara","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tasanee","family":"Onkoksoong","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunisa","family":"Prasopporn","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sith","family":"Sathornsumetee","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siwanon","family":"Jirawatnotai","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uraiwan","family":"Panich","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2249","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"key20261005073039_b1-BR-25-5-02202","doi-asserted-by":"publisher","first-page":"299","DOI":"10.3322\/caac.21613","article-title":"Management of glioblastoma: State of the art and future directions","volume":"70","author":"Tan","year":"2020","journal-title":"CA Cancer J Clin"},{"issue":"762","key":"key20261005073039_b2-BR-25-5-02202","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-023-11271-w","article-title":"Targeting sphingolipid metabolism with the sphingosine kinase inhibitor SKI-II overcomes hypoxia-induced chemotherapy resistance in glioblastoma cells: Effects on cell death, self-renewal, and invasion","volume":"23","author":"Sousa","year":"2023","journal-title":"BMC Cancer"},{"key":"key20261005073039_b3-BR-25-5-02202","doi-asserted-by":"publisher","first-page":"8596","DOI":"10.1021\/acs.jmedchem.1c01946","article-title":"Glioblastoma: Current status, emerging targets, and recent advances","volume":"65","author":"Thakur","year":"2022","journal-title":"J Med Chem"},{"issue":"45","key":"key20261005073039_b4-BR-25-5-02202","doi-asserted-by":"publisher","DOI":"10.3390\/cells6040045","article-title":"The role of hypoxia in glioblastoma invasion","volume":"6","author":"Monteiro","year":"2017","journal-title":"Cells"},{"key":"key20261005073039_b5-BR-25-5-02202","doi-asserted-by":"publisher","first-page":"1516","DOI":"10.1089\/ars.2013.5378","article-title":"The clinical importance of assessing tumor hypoxia: Relationship of tumor hypoxia to prognosis and therapeutic opportunities","volume":"21","author":"Walsh","year":"2014","journal-title":"Antioxid Redox Signal"},{"issue":"1128","key":"key20261005073039_b6-BR-25-5-02202","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-1176-7","article-title":"Hypoxia-mediated mitochondria apoptosis inhibition induces temozolomide treatment resistance through miR-26a\/Bad\/Bax axis","volume":"9","author":"Ge","year":"2018","journal-title":"Cell Death Dis"},{"key":"key20261005073039_b7-BR-25-5-02202","doi-asserted-by":"publisher","first-page":"17","DOI":"10.20517\/cdr.2020.79","article-title":"Mechanisms of temozolomide resistance in glioblastoma-a comprehensive review","volume":"4","author":"Singh","year":"2021","journal-title":"Cancer Drug Resist"},{"issue":"269","key":"key20261005073039_b8-BR-25-5-02202","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-05788-y","article-title":"CEBPD is a master transcriptional factor for hypoxia regulated proteins in glioblastoma and augments hypoxia induced invasion through extracellular matrix-integrin mediated EGFR\/PI3K pathway","volume":"14","author":"Mao","year":"2023","journal-title":"Cell Death Dis"},{"key":"key20261005073039_b9-BR-25-5-02202","doi-asserted-by":"publisher","first-page":"25130","DOI":"10.1074\/jbc.M001914200","article-title":"Reactive oxygen species generated at mitochondrial complex III stabilize hypoxia-inducible factor-1alpha during hypoxia: A mechanism of O2 sensing","volume":"275","author":"Chandel","year":"2000","journal-title":"J Biol Chem"},{"key":"key20261005073039_b10-BR-25-5-02202","doi-asserted-by":"publisher","first-page":"L922","DOI":"10.1152\/ajplung.00014.2002","article-title":"Hypoxic but not anoxic stabilization of HIF-1alpha requires mitochondrial reactive oxygen species","volume":"283","author":"Schroedl","year":"2002","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"key20261005073039_b11-BR-25-5-02202","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/j.cmet.2005.05.001","article-title":"Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing","volume":"1","author":"Guzy","year":"2005","journal-title":"Cell Metab"},{"key":"key20261005073039_b12-BR-25-5-02202","doi-asserted-by":"publisher","first-page":"5197","DOI":"10.1093\/emboj\/20.18.5197","article-title":"Independent function of two destruction domains in hypoxia-inducible factor-alpha chains activated by prolyl hydroxylation","volume":"20","author":"Masson","year":"2001","journal-title":"EMBO J"},{"key":"key20261005073039_b13-BR-25-5-02202","doi-asserted-by":"publisher","first-page":"6415","DOI":"10.1128\/MCB.25.15.6415-6426.2005","article-title":"Coordinate regulation of the oxygen-dependent degradation domains of hypoxia-inducible factor 1 alpha","volume":"25","author":"Chan","year":"2005","journal-title":"Mol Cell Biol"},{"key":"key20261005073039_b14-BR-25-5-02202","doi-asserted-by":"publisher","first-page":"7130","DOI":"10.1128\/MCB.24.16.7130-7139.2004","article-title":"Oxidative stress sensor Keap1 functions as an adaptor for Cul3-based E3 ligase to regulate proteasomal degradation of Nrf2","volume":"24","author":"Kobayashi","year":"2004","journal-title":"Mol Cell Biol"},{"key":"key20261005073039_b15-BR-25-5-02202","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1038\/s12276-024-01180-8","article-title":"Hypoxia, oxidative stress, and the interplay of HIFs and NRF2 signaling in cancer","volume":"56","author":"Bae","year":"2024","journal-title":"Exp Mol Med"},{"key":"key20261005073039_b16-BR-25-5-02202","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1002\/ijc.28699","article-title":"Knockdown of Nrf2 suppresses glioblastoma angiogenesis by inhibiting hypoxia-induced activation of HIF-1\u03b1","volume":"135","author":"Ji","year":"2014","journal-title":"Int J Cancer"},{"key":"key20261005073039_b17-BR-25-5-02202","doi-asserted-by":"publisher","first-page":"4105","DOI":"10.21037\/tcr-22-1420","article-title":"Knockdown of Nrf2 radiosensitizes glioma cells by inducing redox stress and apoptosis in hypoxia","volume":"11","author":"Tang","year":"2022","journal-title":"Transl Cancer Res"},{"key":"key20261005073039_b18-BR-25-5-02202","doi-asserted-by":"publisher","first-page":"1235","DOI":"10.1093\/carcin\/bgn095","article-title":"Nrf2 enhances resistance of cancer cells to chemotherapeutic drugs, the dark side of Nrf2","volume":"29","author":"Wang","year":"2008","journal-title":"Carcinogenesis"},{"key":"key20261005073039_b19-BR-25-5-02202","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1158\/1535-7163.MCT-15-0621","article-title":"The role of PGC1\u03b1 in cancer metabolism and its therapeutic implications","volume":"15","author":"Tan","year":"2016","journal-title":"Mol Cancer Ther"},{"key":"key20261005073039_b20-BR-25-5-02202","doi-asserted-by":"publisher","first-page":"2092","DOI":"10.1002\/1873-3468.14993","article-title":"Nrf2 as a regulator of energy metabolism and mitochondrial function","volume":"598","author":"Luchkova","year":"2024","journal-title":"FEBS Lett"},{"key":"key20261005073039_b21-BR-25-5-02202","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.1073\/pnas.1014275108","article-title":"Brusatol enhances the efficacy of chemotherapy by inhibiting the Nrf2-mediated defense mechanism","volume":"108","author":"Ren","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"key":"key20261005073039_b22-BR-25-5-02202","doi-asserted-by":"publisher","first-page":"1493","DOI":"10.1002\/mc.22609","article-title":"Brusatol overcomes chemoresistance through inhibition of protein translation","volume":"56","author":"Harder","year":"2017","journal-title":"Mol Carcinog"},{"key":"key20261005073039_b23-BR-25-5-02202","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/j.freeradbiomed.2014.11.003","article-title":"Brusatol provokes a rapid and transient inhibition of Nrf2 signaling and sensitizes mammalian cells to chemical toxicity-implications for therapeutic targeting of Nrf2","volume":"78","author":"Olayanju","year":"2015","journal-title":"Free Radic Biol Med"},{"key":"key20261005073039_b24-BR-25-5-02202","doi-asserted-by":"publisher","first-page":"172","DOI":"10.4172\/1948-5956.1000410","article-title":"Anti-VEGFR2 driven nuclear translocation of VEGFR2 and acquired malignant hallmarks are mutation dependent in glioblastoma","volume":"8","author":"Shankar","year":"2016","journal-title":"J Cancer Sci Ther"},{"issue":"877194","key":"key20261005073039_b25-BR-25-5-02202","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.877194","article-title":"The acquired vulnerability caused by CDK4\/6 inhibition promotes drug synergism between oxaliplatin and palbociclib in cholangiocarcinoma","volume":"12","author":"Suppramote","year":"2022","journal-title":"Front Oncol"},{"issue":"649820","key":"key20261005073039_b26-BR-25-5-02202","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.649820","article-title":"The protective effect of polyherbal formulation, harak formula, on UVA-induced photoaging of human dermal fibroblasts and mouse skin via promoting Nrf2-regulated antioxidant defense","volume":"12","author":"Lohakul","year":"2021","journal-title":"Front Pharmacol"},{"key":"key20261005073039_b27-BR-25-5-02202","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"key20261005073039_b28-BR-25-5-02202","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.redox.2015.12.006","article-title":"Photoprotection by dietary phenolics against melanogenesis induced by UVA through Nrf2-dependent antioxidant responses","volume":"8","author":"Chaiprasongsuk","year":"2016","journal-title":"Redox Biol"},{"key":"key20261005073039_b29-BR-25-5-02202","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.freeradbiomed.2023.12.007","article-title":"Live-cell imaging Unveils stimulus-specific dynamics of Nrf2 activation in UV-exposed melanoma cells: Implications for antioxidant compound screening","volume":"211","author":"Htut","year":"2024","journal-title":"Free Radic Biol Med"},{"issue":"642","key":"key20261005073039_b30-BR-25-5-02202","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10050642","article-title":"Oxidative stress in cancer cell metabolism","volume":"10","author":"Arfin","year":"2021","journal-title":"Antioxidants (Basel)"},{"issue":"775680","key":"key20261005073039_b31-BR-25-5-02202","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.775680","article-title":"Brusatol inhibits proliferation and invasion of glioblastoma by down-regulating the expression of ECM1","volume":"12","author":"Dai","year":"2021","journal-title":"Front Pharmacol"},{"key":"key20261005073039_b32-BR-25-5-02202","doi-asserted-by":"publisher","first-page":"6228","DOI":"10.1111\/jcmm.14507","article-title":"Integrated analysis identified core signal pathways and hypoxic characteristics of human glioblastoma","volume":"23","author":"Gao","year":"2019","journal-title":"J Cell Mol Med"},{"key":"key20261005073039_b33-BR-25-5-02202","doi-asserted-by":"publisher","first-page":"4901","DOI":"10.1128\/MCB.00409-10","article-title":"Mechanism of hypoxia-induced NF-kappaB","volume":"30","author":"Culver","year":"2010","journal-title":"Mol Cell Biol"},{"issue":"312","key":"key20261005073039_b34-BR-25-5-02202","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-03598-8","article-title":"HIF1\u03b1\/HIF2\u03b1-Sox2\/Klf4 promotes the malignant progression of glioblastoma via the EGFR-PI3K\/AKT signalling pathway with positive feedback under hypoxia","volume":"12","author":"Wang","year":"2021","journal-title":"Cell Death Dis"},{"issue":"218","key":"key20261005073039_b35-BR-25-5-02202","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01080-1","article-title":"Hypoxia signaling in human health and diseases: Implications and prospects for therapeutics","volume":"7","author":"Luo","year":"2022","journal-title":"Signal Transduc Target Ther"},{"key":"key20261005073039_b36-BR-25-5-02202","doi-asserted-by":"publisher","first-page":"2491","DOI":"10.1002\/ijc.28889","article-title":"The potential role of HIF on tumour progression and dissemination","volume":"136","author":"Unwith","year":"2015","journal-title":"Int J Cancer"},{"key":"key20261005073039_b37-BR-25-5-02202","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.gendis.2016.11.003","article-title":"The role of hypoxia-inducible factors in tumor angiogenesis and cell metabolism","volume":"4","author":"Lv","year":"2016","journal-title":"Genes Dis"},{"issue":"94","key":"key20261005073039_b38-BR-25-5-02202","doi-asserted-by":"publisher","DOI":"10.1007\/s12672-022-00556-4","article-title":"Exploring the role of Nrf2 signaling in glioblastoma multiforme","volume":"13","author":"Awuah","year":"2022","journal-title":"Discov Oncol"},{"issue":"102726","key":"key20261005073039_b39-BR-25-5-02202","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102726","article-title":"The KEAP1-NRF2 pathway: Targets for therapy and role in cancer","volume":"63","author":"Adinolfi","year":"2023","journal-title":"Redox Biol"},{"key":"key20261005073039_b40-BR-25-5-02202","doi-asserted-by":"publisher","first-page":"3029","DOI":"10.7150\/ijbs.82401","article-title":"Natural Nrf2 inhibitors: A review of their potential for cancer treatment","volume":"19","author":"Zhang","year":"2023","journal-title":"Int J Biol Sci"},{"key":"key20261005073039_b41-BR-25-5-02202","author":"Harifi-Mood"},{"key":"key20261005073039_b42-BR-25-5-02202","doi-asserted-by":"publisher","first-page":"14659","DOI":"10.18632\/oncotarget.7406","article-title":"Nrf2 is the key to chemotherapy resistance in MCF7 breast cancer cells under hypoxia","volume":"7","author":"Syu","year":"2016","journal-title":"Oncotarget"},{"issue":"114134","key":"key20261005073039_b43-BR-25-5-02202","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.114134","article-title":"Brusatol: A potential sensitizing agent for cancer therapy from Brucea javanica","volume":"158","author":"He","year":"2023","journal-title":"Biomed Pharmacother"},{"key":"key20261005073039_b44-BR-25-5-02202","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1016\/j.redox.2013.08.002","article-title":"Nrf2 activation supports cell survival during hypoxia and hypoxia\/reoxygenation in cardiomyoblasts; the roles of reactive oxygen and nitrogen species","volume":"1","author":"Kolamunne","year":"2013","journal-title":"Redox Biol"},{"issue":"39123","key":"key20261005073039_b45-BR-25-5-02202","doi-asserted-by":"publisher","DOI":"10.1038\/srep39123","article-title":"Brusatol inhibits HIF-1 signaling pathway and suppresses glucose uptake under hypoxic conditions in HCT116 cells","volume":"6","author":"Lu","year":"2016","journal-title":"Sci Rep"},{"key":"key20261005073039_b46-BR-25-5-02202","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/j.molmed.2015.04.001","article-title":"EGFR and NF-\u03baB: Partners in cancer","volume":"21","author":"Shostak","year":"2015","journal-title":"Trends Mol Med"},{"issue":"786728","key":"key20261005073039_b47-BR-25-5-02202","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.786728","article-title":"TGF-\u03b2 signaling and resistance to cancer therapy","volume":"9","author":"Zhang","year":"2021","journal-title":"Front Cell Dev Biol"},{"issue":"2748","key":"key20261005073039_b48-BR-25-5-02202","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13112748","article-title":"EGFR in cancer: Signaling mechanisms, drugs, and acquired resistance","volume":"13","author":"Uribe","year":"2021","journal-title":"Cancers (Basel)"},{"issue":"438","key":"key20261005073039_b49-BR-25-5-02202","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-022-01230-y","article-title":"Characterization of EGFR-reprogrammable temozolomide-resistant cells in a model of glioblastoma","volume":"8","author":"Gong","year":"2022","journal-title":"Cell Death Discov"},{"issue":"6823471","key":"key20261005073039_b50-BR-25-5-02202","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/6823471","article-title":"TGF-\u03b2 and hypoxia\/reoxygenation promote radioresistance of A549 lung cancer cells through activation of Nrf2 and EGFR","volume":"2016","author":"Lee","year":"2016","journal-title":"Oxid Med Cell Longev"},{"key":"key20261005073039_b51-BR-25-5-02202","doi-asserted-by":"publisher","first-page":"129","DOI":"10.4062\/biomolther.2024.084","article-title":"6-Gingerol induced apoptosis and cell cycle arrest in glioma cells via MnSOD and ERK phosphorylation modulation","volume":"33","author":"Lim","year":"2025","journal-title":"Biomol Ther (Seoul)"},{"key":"key20261005073039_b52-BR-25-5-02202","doi-asserted-by":"publisher","first-page":"16983","DOI":"10.1074\/jbc.M117.792838","article-title":"Insulin-like growth factor 1 signaling is essential for mitochondrial biogenesis and mitophagy in cancer cells","volume":"292","author":"Lyons","year":"2017","journal-title":"J Biol Chem"}],"container-title":["Biomedical Reports"],"original-title":[],"deposited":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:30:51Z","timestamp":1791174651000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.spandidos-publications.com\/10.3892\/br.2026.2202"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,11]]},"references-count":52,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,9,11]]}},"URL":"https:\/\/doi.org\/10.3892\/br.2026.2202","relation":{},"ISSN":["2049-9434","2049-9442"],"issn-type":[{"value":"2049-9434","type":"print"},{"value":"2049-9442","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,11]]}}}