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Atorvastatin Promotes Cytotoxicity and Reduces Migration and Proliferation of Human A172 Glioma Cells

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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.

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Acknowledgements

This study was supported by grants from the Brazilian funding agencies Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (Universal/2012; INCT), Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina (FAPESC) (NENASC/PRONEX), and Coordenação de Aperfeiçoamento de Pessoal de Ensino Superior (CAPES) (PVE-052/2012) to C.I.T. and CNPq (Universal/2013) to C.B.N. T.D.-C. was recipient of a CAPES/PVE post-doctoral fellowship, and C.I.T. is recipient of CNPq productivity fellowship.

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  1. Programa de Pós-Graduação em Bioquímica, Florianópolis, Brazil

    Karen A. Oliveira, Fabiana K. Ludka & Carla I. Tasca

  2. Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, 88040900, Florianópolis, Brazil

    Karen A. Oliveira, Fabiana K. Ludka & Carla I. Tasca

  3. Programa de Pós-Graduação em Neurociências, Florianópolis, Brazil

    Tharine Dal-Cim, Cláudia B. Nedel & Carla I. Tasca

  4. Departamento de Biologia Celular, Embriologia e Genética, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, 88040-900, Brazil

    Flávia G. Lopes & Cláudia B. Nedel

  5. Curso de Farmácia, Universidade do Contestado, Canoinhas, Brazil

    Fabiana K. Ludka

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Oliveira, K.A., Dal-Cim, T., Lopes, F.G. et al. Atorvastatin Promotes Cytotoxicity and Reduces Migration and Proliferation of Human A172 Glioma Cells. Mol Neurobiol 55, 1509–1523 (2018). https://doi.org/10.1007/s12035-017-0423-8

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