Vitamin C deficient reduces proliferation in a human periventricular tumor stem cell-derived glioblastoma model.
J Cell Physiol
; 236(8): 5801-5817, 2021 08.
Article
em En
| MEDLINE
| ID: mdl-33432597
Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor with a median survival of 14.6 months. GBM is highly resistant to radio- 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-MG or HSVT-C3 cells) in the subventricular zone of guinea pig brain. Initial characterization of U87-MG and HSVT-C3 cells showed that HSVT-C3 are highly proliferative, overexpress p53, and are resistant to ferroptosis. To induce intraperiventricular tumors, animals received control or a vitamin C-deficient diet for 3 weeks, after which histopathological and confocal microscopy analyses were performed. We demonstrated that the vitamin C-deficient condition reduced the glomeruloid vasculature and microglia/macrophage infiltration in U87-MG tumors. Furthermore, tumor size, proliferation, glomeruloid vasculature, microglia/macrophage infiltration, and invasion were reduced in C3 tumors carried by vitamin C-deficient guinea pigs. In conclusion, the effect of the vitamin C deficiency was dependent on the tumor cell used for GBM induction. HSVT-C3 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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Deficiência de Ácido Ascórbico
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Células-Tronco Neoplásicas
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Glioblastoma
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Proliferação de Células
Limite:
Animals
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Humans
Idioma:
En
Revista:
J Cell Physiol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Chile
País de publicação:
Estados Unidos