Impact of gamma linolenic and arachidonic acids associated with temozolamide on the regulation of Murine Glioblastoma cellular behavior
Abstract: Glioblastomas (GBs) are the most common primary tumors of the central nervous system. The first-line treatment is surgical resection complemented with chemo and radiotherapy, but due to its late diagnosis and its infiltrative characteristic the survival is low. The chemother...
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| Autores principales: | , , , , , , |
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| Formato: | Artículo revista |
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Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología
2021
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| Acceso en línea: | https://revistas.unc.edu.ar/index.php/med/article/view/34948 |
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| Sumario: | Abstract:
Glioblastomas (GBs) are the most common primary tumors of the central nervous system. The first-line treatment is surgical resection complemented with chemo and radiotherapy, but due to its late diagnosis and its infiltrative characteristic the survival is low. The chemotherapy used in most GBs is Temozolomide (TMZ). As a second line, other chemotherapeutic agents and oncolytic virotherapy are used. It is known that omega-6 polyunsaturated fatty acids (PUFAs) have a high therapeutic potential in GBs treatment since they exhibit tumoricidal activity without significant side effects. In the present work we study the effects of two omega-6 PUFAs: arachidonic acid (AA, 20:04) and gamma linolenic acid (GLA, 18:03) associated with TMZ on cell viability and proliferation and their relationship with p53 expression in a murine glioblastoma cell line (GL26). The cells were treated with: AA, GLA, TMZ, AA + TMZ or GLA + TMZ [10, 20, 30, 40, 50 and 100 µM] and ethanol (control). We evaluate cell viability by fluorimetry with resazurin; cell proliferation with Ki67 and p53 expression by immunocytochemistry. Lipid cell profile by gas chromatography (GC) and generation of eicosanoids by high pressure liquid chromatography (HPLC). Statistical analysis was performed using the Kruskal Wallis test. Our results show that AA + TMZ and GLA + TMZ significantly reduce the viability compared to TMZ (p <0.05). GLA, TMZ and GLA + TMZ significantly reduce the expression of Ki67 (p <0.01) and increase the expression of p53 (p <0.1) with respect to the control. The percentages of AA and GLA are higher in GL26 cell membranes treated with AA and GLA respectively in relation to cells treated with TMZ. GLA reduce the release of 12-HHT compared to the control. TMZ combined with GLA exerts an antiproliferative effect by decreasing the release of 12-HHT and increasing the expression of p53.
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