Atorvastatin Promotes Cytotoxicity and Reduces Migration and Proliferation of Human A172 Glioma Cells.
Mol Neurobiol
; 55(2): 1509-1523, 2018 02.
Article
en En
| MEDLINE
| ID: mdl-28181188
ABSTRACT
Malignant gliomas have resistance mechanisms to chemotherapy that enable tumor invasiveness and aggressiveness. Alternative therapies in cancer treatment, as statins, have been suggested to decrease proliferation, inhibit cell migration, and induce cell death. The aim of this study was to evaluate the effect of atorvastatin (ATOR) on cell viability, migration, proliferation, apoptosis, and autophagy in A172 human glioma cells. Temozolomide (TMZ), a chemotherapic used to glioma treatment, was tested as a comparison to cytotoxic effects on gliomas. Cell viability was also assessed in primary culture of cortical astrocytes. ATOR treatment (0.1 to 20 µM) did not alter astrocytic viability. However, in glioma cells, ATOR showed cytotoxic effect at 10 and 20 µM concentrations. TMZ (500 µM) reduced cell viability similarly to ATOR, and drug association did not show additive effect on cell viability. ATOR, TMZ, and their association decreased cell migration. ATOR also decreased glioma cell proliferation. ATOR increased apoptosis, and TMZ association showed a potentiation effect, enhancing it. ATOR and TMZ treatment increased acidic vesicular organelle (AVO) presence in A172 cells, an indicative of autophagy. ATOR effect of reducing A172 cell viability did not alter glutamate transport and glutamine synthetase activity, but it was partially prevented through antagonism of ionotropic and metabotropic glutamate receptors. Our data shows a cytotoxic effect of ATOR on glioma cells, whereas no toxicity was observed to astrocytes. ATOR showed similar cytotoxic effect as TMZ to glioma cells, and it may be a safer drug, regarding side effect induction, than chemotherapic agents.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
6_brain_nervous_system_cancer
Asunto principal:
Neoplasias Encefálicas
/
Movimiento Celular
/
Supervivencia Celular
/
Inhibidores de Hidroximetilglutaril-CoA Reductasas
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Proliferación Celular
/
Atorvastatina
/
Glioma
Límite:
Humans
Idioma:
En
Revista:
Mol Neurobiol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Brasil