{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T11:32:37Z","timestamp":1776511957288,"version":"3.51.2"},"reference-count":71,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T00:00:00Z","timestamp":1728432000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The most common and aggressive brain cancer, glioblastoma, is characterized by hypoxia and poor survival. The pro\u2010tumour transcription factor, hypoxia\u2010inducible factor (HIF), is regulated via HIF\u2010hydroxylases that require ascorbate as cofactor. Decreased HIF\u2010hydroxylase activity triggers the hypoxic pathway driving cancer progression. Tissue ascorbate accumulates via the sodium\u2010dependent vitamin C transporter\u20102 (SVCT2). We hypothesize that glioblastoma cells rely on SVCT2 for ascorbate accumulation, and that knockout of this transporter would disrupt the regulation of the hypoxic pathway by ascorbate. Ascorbate uptake was measured in glioblastoma cell lines (U87MG, U251MG, T98G) by high\u2010performance liquid chromatography. CRISPR\/Cas9 was used to knockout SVCT2. Cells were treated with cobalt chloride, desferrioxamine or 5% oxygen, with\/without ascorbate, and key hypoxic pathway proteins were measured using Western blot analysis. Ascorbate uptake was cell line dependent, ranging from 1.7 to 11.0\u2009nmol\/10<jats:sup>6<\/jats:sup> cells. SVCT2\u2010knockout cells accumulated 90%\u201395% less intracellular ascorbate than parental cells. The hypoxic pathway was induced by all three stimuli, and ascorbate reduced this induction. In the SVCT2\u2010knockout cells, ascorbate had limited effect on the hypoxic pathway. This study verifies that intracellular ascorbate is required to suppress the hypoxic pathway. As patient survival is related to an activated hypoxic pathway, increasing intra\u2010tumoral ascorbate may be of clinical interest.<\/jats:p>","DOI":"10.1002\/jcb.30658","type":"journal-article","created":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T10:45:58Z","timestamp":1728470758000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Role of Sodium\u2010Dependent Vitamin C Transporter\u20102 and Ascorbate in Regulating the Hypoxic Pathway in Cultured Glioblastoma Cells"],"prefix":"10.1002","volume":"126","author":[{"given":"Eleanor R.","family":"Burgess","sequence":"first","affiliation":[{"name":"Mackenzie Cancer Research Group, Department of Pathology and Biomedical Science University of Otago Christchurch Christchurch New Zealand"},{"name":"Department of Immunobiochemistry, Mannheim Institute for Innate Immunology (MI3) Heidelberg University, Medical Faculty Mannheim Mannheim Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Citra","family":"Praditi","sequence":"additional","affiliation":[{"name":"Mackenzie Cancer Research Group, Department of Pathology and Biomedical Science University of Otago Christchurch Christchurch New Zealand"},{"name":"M\u0101tai H\u0101ora, Centre for Redox Biology and Medicine, Department of Pathology and Biomedical Science University of Otago Christchurch Christchurch New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabeth","family":"Phillips","sequence":"additional","affiliation":[{"name":"Mackenzie Cancer Research Group, Department of Pathology and Biomedical Science University of Otago Christchurch Christchurch New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margreet C. 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