Role of Sodium-Dependent Vitamin C Transporter-2 and Ascorbate in Regulating the Hypoxic Pathway in Cultured Glioblastoma Cells.

ABSTRACT: The most common and aggressive brain cancer, glioblastoma, is characterized by hypoxia and poor survival. The pro-tumour transcription factor, hypoxia-inducible factor (HIF), is regulated via HIF-hydroxylases that require ascorbate as cofactor. Decreased HIF-hydroxylase activity triggers the hypoxic pathway driving cancer progression. Tissue ascorbate accumulates via the sodium-dependent vitamin C transporter-2 (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-performance liquid chromatography. CRISPR/Cas9 was used to knockout SVCT2. Cells were treated with cobal

SUBMITTER: Burgess ER 

PROVIDER: S-EPMC11729540 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature