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Analysis of the oxidative stress induced by sulfasalazine associated with temozolomide in human and rat glioma cells

Abstract

Gliomas are the most common adult brain tumors. High-grade astrocytomas are astrocyte-derived gliomas, which pathogenesis includes overexpression of the epidermal growth factor receptor (EGFR) and loss of p53 and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) protein function. Such proteins regulate cell cycle and DNA stability. Additionally, it has been described that gliomas show increased concentration of the antioxidant glutathione(GSH), which would protect cells from redox stress. Astrocytes - the neoplastic ones mainly - express a cytoplasmic membrane transporter (system Xc-) that imports cystine for GSH synthesis and releases glutamate. The latter event would induce excitotoxicity and death in peritumoral cells, thus favoring tumor invasion. Neoplastic invasion also involves degradation of extracellular matrix by metalloproteinases 2 and 9 (MMP-2 and 9). The DNA alkylating agent temozolomide (TMZ) has been used in the treatment of patients with high-grade gliomas. However, their clinical outcome has invariably been fatal. In the present study, we aim to study the viability of glioma cell lines (U87-MG, T98G, A172 and C6) treated with TMZ and/or sulfasalazine (SAS), an inhibitor of the system Xc-. Moreover, we will evaluate EGFR, PTEN, TP53, MMP-2 and MMP-9 gene expression in and invasive capacity of treated cells. Our intention is to contribute to the understanding of gliomagenesis and investigate new therapeutic approaches to glioma treatment. (AU)

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Scientific publications (4)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
FACCHINI, GUSTAVO; IGNARRO, RAFFAELA SILVESTRE; RODRIGUES-SILVA, ERIKA; VIEIRA, ANDRE SCHWAMBACH; LOPES-CENDES, ISCIA; CASTILHO, ROGER FRIGERIO; ROGERIO, FABIO. Toxic effects of phytol and retinol on human glioblastoma cells are associated with modulation of cholesterol and fatty acid biosynthetic pathways. JOURNAL OF NEURO-ONCOLOGY, v. 136, n. 3, p. 435-443, FEB 2018. Web of Science Citations: 4.
RODRIGUES-SILVA, ERIKA; SIQUEIRA-SANTOS, EDILENE S.; RUAS, JULIANA S.; IGNARRO, RAFFAELA S.; FIGUEIRA, TIAGO R.; ROGERIO, FABIO; CASTILHO, ROGER F. Evaluation of mitochondrial respiratory function in highly glycolytic glioma cells reveals low ADP phosphorylation in relation to oxidative capacity. JOURNAL OF NEURO-ONCOLOGY, v. 133, n. 3, p. 519-529, JUL 2017. Web of Science Citations: 3.
IGNARRO, RAFFAELA SILVESTRE; FACCHINI, GUSTAVO; DE MELO, DANIELA RODRIGUES; PELIZZARO-ROCHA, KARIN JULIANE; FERREIRA, CARMEN VERISSIMA; CASTILHO, ROGER FRIGERIO; ROGERIO, FABIO. Characteristics of sulfasalazine-induced cytotoxicity in C6 rat glioma cells. Neuroscience Letters, v. 638, p. 189-195, JAN 18 2017. Web of Science Citations: 3.
IGNARRO, RAFFAELA SILVESTRE; FACCHINI, GUSTAVO; VIEIRA, ANDRE SCHWAMBACH; DE MELO, DANIELA RODRIGUES; LOPES-CENDES, ISCIA; CASTILHO, ROGER FRIGERIO; ROGERIO, FABIO. Sulfasalazine intensifies temozolomide cytotoxicity in human glioblastoma cells. Molecular and Cellular Biochemistry, v. 418, n. 1-2, p. 167-178, JUL 2016. Web of Science Citations: 6.

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