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Temozolomide, quercetin and cell death in the MOGGCCM astrocytoma cell line.

Summary of "Temozolomide, quercetin and cell death in the MOGGCCM astrocytoma cell line."

The aim of the present study was to investigate the effect of Temozolomide (an alkylating chemotherapeutic agent) and quercetin (natural flavonoid) on cell death in the human astrocytoma cell line MOGGCCM (WHO grade III). Our results indicate that Temozolomide induces autophagy, while quercetin promotes severe necrosis in the cell line in a manner dependent on the drug concentration. We demonstrated for the first time that combinations of both drugs were much more effective in programmed cell death induction in glioma cells. At a low (5muM) drug concentration, quercetin potentiated a pro-autophagic effect of Temozolomide, while after treatment with a higher drug concentration (30muM), autophagy switched to apoptosis. Temozolomide attenuated the toxic effect of quercetin. Apoptosis was mediated by the mitochondrial pathway and the activation of caspase 3 and cytochrome C release, but no changes in caspase 8 expression was observed. It was accompanied by decreased mitochondrial membrane potential and inhibition of Hsp27 and Hsp72 expression. Autophagy was correlated with an increased level of LC3II. Temozolomide and quercetin also inhibited migratory phenotype of MOGGCCM cells and changed the nuclei morphology from a circular to an irregular shape. Our results indicate that quercetin acts in synergy with Temozolomide and when used in combination rather than in separate pharmacological application, both drugs are more effective in programmed cell death induction. Temozolomide administered with quercetin seems to be a potent and promising combination which might be useful in glioma therapy.

Affiliation

Department of Comparative Anatomy and Anthropology, Maria Curie-Sklodowska University, Akademicka 19, 20-033 Lublin, Poland. jjgil@poczta.umcs.lublin.pl

Journal Details

This article was published in the following journal.

Name: Chemico-biological interactions
ISSN: 1872-7786
Pages: 190-203

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Medical and Biotech [MESH] Definitions

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A large family of receptor protein-tyrosine kinases that are structurally-related. The name of this family of proteins derives from original protein Eph (now called the EPHA1 RECEPTOR), which was named after the cell line it was first discovered in: Erythropoietin-Producing human Hepatocellular carcinoma cell line. Members of this family have been implicated in regulation of cell-cell interactions involved in nervous system patterning and development.

A cell line established in 1962 from disaggregated Swiss albino mouse embryos. This fibroblast cell line is extremely popular in research.

A cell line derived from cultured tumor cells.

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