Impact of gamma linolenic and arachidonic acids associated with temozolamide on the regulation of Murine Glioblastoma cellular behavior

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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:	Depetris , S, Barotto , NN, Sandrone , SS, Garay , MI, Hollman , CH, Brunotto , MN, Pasqualini , ME
Formato:	Artículo revista
Publicado:	Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología 2021
Materias:	glioblastomas (GBs gamma linolenic acid (GLA) arachidonic acid (AA) temozolomide (TMZ) transcription factor p53 (p53) Glioblastomas (GBs) Acido gama linolenico (GLA) Acido araquidónico (AA) Temozolomida (TMZ) factor de transcripción p53 (p53) .
Acceso en línea:	https://revistas.unc.edu.ar/index.php/med/article/view/34948
Aporte de:	Revista de la Facultad de Ciencias Médicas de Córdoba de Universidad Nacional de Córdoba

id	I10-R327-article-34948
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institution	Universidad Nacional de Córdoba
institution_str	I-10
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container_title_str	Revista de la Facultad de Ciencias Médicas de Córdoba
format	Artículo revista
topic	glioblastomas (GBs gamma linolenic acid (GLA) arachidonic acid (AA) temozolomide (TMZ) transcription factor p53 (p53) Glioblastomas (GBs) Acido gama linolenico (GLA) Acido araquidónico (AA) Temozolomida (TMZ) factor de transcripción p53 (p53) .
spellingShingle	glioblastomas (GBs gamma linolenic acid (GLA) arachidonic acid (AA) temozolomide (TMZ) transcription factor p53 (p53) Glioblastomas (GBs) Acido gama linolenico (GLA) Acido araquidónico (AA) Temozolomida (TMZ) factor de transcripción p53 (p53) . Depetris , S Barotto , NN Sandrone , SS Garay , MI Hollman , CH Brunotto , MN Pasqualini , ME Impact of gamma linolenic and arachidonic acids associated with temozolamide on the regulation of Murine Glioblastoma cellular behavior
topic_facet	glioblastomas (GBs gamma linolenic acid (GLA) arachidonic acid (AA) temozolomide (TMZ) transcription factor p53 (p53) Glioblastomas (GBs) Acido gama linolenico (GLA) Acido araquidónico (AA) Temozolomida (TMZ) factor de transcripción p53 (p53) .
author	Depetris , S Barotto , NN Sandrone , SS Garay , MI Hollman , CH Brunotto , MN Pasqualini , ME
author_facet	Depetris , S Barotto , NN Sandrone , SS Garay , MI Hollman , CH Brunotto , MN Pasqualini , ME
author_sort	Depetris , S
title	Impact of gamma linolenic and arachidonic acids associated with temozolamide on the regulation of Murine Glioblastoma cellular behavior
title_short	Impact of gamma linolenic and arachidonic acids associated with temozolamide on the regulation of Murine Glioblastoma cellular behavior
title_full	Impact of gamma linolenic and arachidonic acids associated with temozolamide on the regulation of Murine Glioblastoma cellular behavior
title_fullStr	Impact of gamma linolenic and arachidonic acids associated with temozolamide on the regulation of Murine Glioblastoma cellular behavior
title_full_unstemmed	Impact of gamma linolenic and arachidonic acids associated with temozolamide on the regulation of Murine Glioblastoma cellular behavior
title_sort	impact of gamma linolenic and arachidonic acids associated with temozolamide on the regulation of murine glioblastoma cellular behavior
description	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.
publisher	Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología
publishDate	2021
url	https://revistas.unc.edu.ar/index.php/med/article/view/34948
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spelling	I10-R327-article-349482024-04-15T16:19:09Z Impact of gamma linolenic and arachidonic acids associated with temozolamide on the regulation of Murine Glioblastoma cellular behavior Impacto de los ácidos grasos gama linolenico y araquidónico asociados a temozolamida en la regulación del comportamiento celular de un Glioblastoma Murino A Depetris , S Barotto , NN Sandrone , SS Garay , MI Hollman , CH Brunotto , MN Pasqualini , ME glioblastomas (GBs gamma linolenic acid (GLA) arachidonic acid (AA) temozolomide (TMZ) transcription factor p53 (p53) Glioblastomas (GBs) Acido gama linolenico (GLA) Acido araquidónico (AA) Temozolomida (TMZ) factor de transcripción p53 (p53) . 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. Resumen:  Los gliobastomas (GBs) son los tumores primarios más frecuentes del sistema nervioso central. El tratamiento de primera línea es la resección quirúrgica  complementada con quimio y radioterapia pero por su diagnóstico tardío y su poder infiltrativo la supervivencia es baja. El quimioterápico usado en la mayoría de los GBs es la Temozolomida (TMZ). Como segunda línea se emplean otros quimioterapéuticos y viroterapia oncolítica. Se conoce que los ácidos grasos poliinsaturados (AGPs) de la familia omega-6 tienen un alto potencial terapéutico en el tratamiento de GBs ya que exhiben actividad tumoricida sin presentar  efectos secundarios significativos. En el presente trabajo estudiamos los efectos de dos AGPs omega-6: el ácido araquidónico (AA, 20:04) y el ácido gama linolénico (GLA, 18:03) asociados a TMZ sobre la viabilidad y proliferación celular y su relación con la expresión de p53 en una línea celular de glioblastoma murina (GL26). Las células fueron tratadas con: AA, GLA, TMZ, AA+TMZ o GLA+TMZ [10, 20, 30, 40, 50 y 100 µM] y etanol  (control).   Evaluamos viabilidad celular por fluorimetría con resazurina; proliferación celular con Ki67 y expresión de p53 por inmunocitoquímica; perfil celular lipídico por cromatografía de gases (GC) y generación de eicosanoides por cromatografía líquida de alta presión (HPLC). El análisis estadístico se realizó mediante la prueba de Kruskal Wallis. Nuestros resultados mostraron que AA+TMZ y GLA+TMZ redujeron significativamente la viabilidad respecto a TMZ (p<0.05). GLA, TMZ y GLA+TMZ redujeron significativamente la expresión de KI67 (p<0.01) y aumentaron la expresión de p53 (p<0.1) con respecto al control. Los porcentajes de AA y GLA fueron mayores en membranas de células GL26 tratadas con AA y GLA respectivamente en relación a las tratadas con TMZ.  GLA redujo la liberación del eicosanoide 12-HHT respecto al control. La TMZ combinada con GLA ejerce un efecto antiproliferativo disminuyendo la liberación de 12-HHT y aumentando la expresión de p53. . Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología 2021-10-12 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion texto texto texto https://revistas.unc.edu.ar/index.php/med/article/view/34948 Revista de la Facultad de Ciencias Médicas de Córdoba.; Vol. 78 No. Suplemento (2021): Suplemento JIC XXII Revista de la Facultad de Ciencias Médicas de Córdoba; Vol. 78 Núm. Suplemento (2021): Suplemento JIC XXII Revista da Faculdade de Ciências Médicas de Córdoba; v. 78 n. Suplemento (2021): Suplemento JIC XXII 1853-0605 0014-6722 http://creativecommons.org/licenses/by-nc/4.0

Impact of gamma linolenic and arachidonic acids associated with temozolamide on the regulation of Murine Glioblastoma cellular behavior

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