Involvement of N-methylpurine DNA glycosylase in resistance to temozolomide in patient-derived glioma cells

Abstract Chemotherapy for high-grade astrocytic tumors is mainly based on the use of temozolomide (TMZ), whose efficacy is limited by resistance mechanisms. Despite many investigations pointing to O6-methylguanine-DNA-methyltransferase (MGMT) as being responsible for tumor chemo-resistance, its expr...

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Autores principales:	Gemma Serrano-Heras, Beatriz Castro-Robles, Carlos M. Romero-Sánchez, Blanca Carrión, Rosa Barbella-Aponte, Hernán Sandoval, Tomás Segura
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dae88f83974f4fc9a5df3c7c493518eb
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spelling	oai:doaj.org-article:dae88f83974f4fc9a5df3c7c493518eb2021-12-02T13:58:11ZInvolvement of N-methylpurine DNA glycosylase in resistance to temozolomide in patient-derived glioma cells10.1038/s41598-020-78868-02045-2322https://doaj.org/article/dae88f83974f4fc9a5df3c7c493518eb2020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78868-0https://doaj.org/toc/2045-2322Abstract Chemotherapy for high-grade astrocytic tumors is mainly based on the use of temozolomide (TMZ), whose efficacy is limited by resistance mechanisms. Despite many investigations pointing to O6-methylguanine-DNA-methyltransferase (MGMT) as being responsible for tumor chemo-resistance, its expression does not predict an accurate response in most gliomas, suggesting that MGMT is not the only determinant of response to treatment. In this sense, several reports indicate that N-methylpurine-DNA-glycosylase (MPG) may be involved in that resistance. With that in mind, we evaluated for the first time the degree of resistance to TMZ treatment in 18 patient-derived glioma cells and its association with MGMT and MPG mRNA levels. Viability cell assays showed that TMZ treatment hardly caused growth inhibition in the patient-derived cells, even in high concentrations, indicating that all primary cultures were chemo-resistant. mRNA expression analyses showed that the TMZ-resistant phenotype displayed by cells is associated with an elevated expression of MPG to a greater extent than it is with transcript levels of MGMT. Our findings suggest that not only is MGMT implicated in resistance to TMZ but MPG, the first enzyme in base excision repair processing, is also involved, supporting its potential role as a target in anti-resistance chemotherapy for astrocytoma and glioblastoma.Gemma Serrano-HerasBeatriz Castro-RoblesCarlos M. Romero-SánchezBlanca CarriónRosa Barbella-AponteHernán SandovalTomás SeguraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-10 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Gemma Serrano-Heras Beatriz Castro-Robles Carlos M. Romero-Sánchez Blanca Carrión Rosa Barbella-Aponte Hernán Sandoval Tomás Segura Involvement of N-methylpurine DNA glycosylase in resistance to temozolomide in patient-derived glioma cells
description	Abstract Chemotherapy for high-grade astrocytic tumors is mainly based on the use of temozolomide (TMZ), whose efficacy is limited by resistance mechanisms. Despite many investigations pointing to O6-methylguanine-DNA-methyltransferase (MGMT) as being responsible for tumor chemo-resistance, its expression does not predict an accurate response in most gliomas, suggesting that MGMT is not the only determinant of response to treatment. In this sense, several reports indicate that N-methylpurine-DNA-glycosylase (MPG) may be involved in that resistance. With that in mind, we evaluated for the first time the degree of resistance to TMZ treatment in 18 patient-derived glioma cells and its association with MGMT and MPG mRNA levels. Viability cell assays showed that TMZ treatment hardly caused growth inhibition in the patient-derived cells, even in high concentrations, indicating that all primary cultures were chemo-resistant. mRNA expression analyses showed that the TMZ-resistant phenotype displayed by cells is associated with an elevated expression of MPG to a greater extent than it is with transcript levels of MGMT. Our findings suggest that not only is MGMT implicated in resistance to TMZ but MPG, the first enzyme in base excision repair processing, is also involved, supporting its potential role as a target in anti-resistance chemotherapy for astrocytoma and glioblastoma.
format	article
author	Gemma Serrano-Heras Beatriz Castro-Robles Carlos M. Romero-Sánchez Blanca Carrión Rosa Barbella-Aponte Hernán Sandoval Tomás Segura
author_facet	Gemma Serrano-Heras Beatriz Castro-Robles Carlos M. Romero-Sánchez Blanca Carrión Rosa Barbella-Aponte Hernán Sandoval Tomás Segura
author_sort	Gemma Serrano-Heras
title	Involvement of N-methylpurine DNA glycosylase in resistance to temozolomide in patient-derived glioma cells
title_short	Involvement of N-methylpurine DNA glycosylase in resistance to temozolomide in patient-derived glioma cells
title_full	Involvement of N-methylpurine DNA glycosylase in resistance to temozolomide in patient-derived glioma cells
title_fullStr	Involvement of N-methylpurine DNA glycosylase in resistance to temozolomide in patient-derived glioma cells
title_full_unstemmed	Involvement of N-methylpurine DNA glycosylase in resistance to temozolomide in patient-derived glioma cells
title_sort	involvement of n-methylpurine dna glycosylase in resistance to temozolomide in patient-derived glioma cells
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/dae88f83974f4fc9a5df3c7c493518eb
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Involvement of N-methylpurine DNA glycosylase in resistance to temozolomide in patient-derived glioma cells

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