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GBM is highly resistant to radio\u2010 and chemotherapy, and remains without a cure; hence, new treatment strategies are constantly sought. Vitamin C, an essential micronutrient and antioxidant, was initially described as an antitumor molecule; however, several studies have shown that it can promote tumor progression and angiogenesis. Thus, considering the high concentrations of vitamin C present in the brain, our aim was to study the effect of vitamin C deficiency on the progression of GBM using a GBM model generated by the stereotactic injection of human GBM cells (U87\u2010MG or HSVT\u2010C3 cells) in the subventricular zone of guinea pig brain. Initial characterization of U87\u2010MG and HSVT\u2010C3 cells showed that HSVT\u2010C3 are highly proliferative, overexpress p53, and are resistant to ferroptosis. To induce intraperiventricular tumors, animals received control or a vitamin C\u2010deficient diet for 3 weeks, after which histopathological and confocal microscopy analyses were performed. We demonstrated that the vitamin C\u2010deficient condition reduced the glomeruloid vasculature and microglia\/macrophage infiltration in U87\u2010MG tumors. Furthermore, tumor size, proliferation, glomeruloid vasculature, microglia\/macrophage infiltration, and invasion were reduced in C3 tumors carried by vitamin C\u2010deficient guinea pigs. In conclusion, the effect of the vitamin C deficiency was dependent on the tumor cell used for GBM induction. HSVT\u2010C3 cells, a cell line with stem cell features isolated from a human subventricular GBM, showed higher sensitivity to the deficient condition; however, vitamin C deficiency displayed an antitumor effect in both GBM models analyzed.<\/jats:p>","DOI":"10.1002\/jcp.30264","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T06:58:27Z","timestamp":1610693907000},"page":"5801-5817","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Vitamin C deficient reduces proliferation in a human periventricular tumor stem cell\u2010derived glioblastoma model"],"prefix":"10.1002","volume":"236","author":[{"given":"Nery","family":"Jara","sequence":"first","affiliation":[{"name":"Department of Cellular Biology, Laboratory of Neurobiology and Stem Cells NeuroCellT, Faculty of Biological Sciences University of Concepcion  Concepcion Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eder","family":"Ramirez","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology, Laboratory of Neurobiology and Stem Cells NeuroCellT, Faculty of Biological Sciences University of Concepcion  Concepcion Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luciano","family":"Ferrada","sequence":"additional","affiliation":[{"name":"Faculty of Biological Sciences, Center for Advanced Microscopy CMA BIO BIO University of Concepcion  Concepcion Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katterine","family":"Salazar","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology, Laboratory of Neurobiology and Stem Cells NeuroCellT, Faculty of Biological Sciences University of Concepcion  Concepcion Chile"},{"name":"Faculty of Biological Sciences, Center for Advanced Microscopy CMA BIO BIO University of Concepcion  Concepcion Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisca","family":"Espinoza","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology, Laboratory of Neurobiology and Stem Cells NeuroCellT, Faculty of Biological Sciences University of Concepcion  Concepcion Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iv\u00e1n","family":"Gonz\u00e1lez\u2010Chavarr\u00eda","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Laboratory of Biotechnology and Biopharmaceuticals, Faculty of Biological Sciences University of Concepcion  Concepcion Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7762-1417","authenticated-orcid":false,"given":"Francisco","family":"Nualart","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology, Laboratory of Neurobiology and Stem Cells NeuroCellT, Faculty of Biological Sciences University of Concepcion  Concepcion Chile"},{"name":"Faculty of Biological Sciences, Center for Advanced Microscopy CMA BIO BIO University of Concepcion  Concepcion Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,1,11]]},"reference":[{"issue":"18","key":"e_1_2_9_2_1","first-page":"4555","article-title":"Stromal cell oxidation: A mechanism by which tumors obtain vitamin C","volume":"59","author":"Agus D. 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