GADD45A plays a protective role against temozolomide treatment in glioblastoma cells

Abstract Glioblastoma multiforme (GBM) is one of the most aggressive cancers. Despite recent advances in multimodal therapies, high-grade glioma remains fatal. Temozolomide (TMZ) is an alkylating agent used worldwide for the clinical treatment of GBM; however, the innate and acquired resistance of G...

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Autores principales:	Hsiao-Han Wang, Tsuey-Yu Chang, Wei-Chen Lin, Kuo-Chen Wei, Jyh-Wei Shin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1ee0ffa440bc41b78b22d295136c806d
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spelling	oai:doaj.org-article:1ee0ffa440bc41b78b22d295136c806d2021-12-02T16:06:12ZGADD45A plays a protective role against temozolomide treatment in glioblastoma cells10.1038/s41598-017-06851-32045-2322https://doaj.org/article/1ee0ffa440bc41b78b22d295136c806d2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06851-3https://doaj.org/toc/2045-2322Abstract Glioblastoma multiforme (GBM) is one of the most aggressive cancers. Despite recent advances in multimodal therapies, high-grade glioma remains fatal. Temozolomide (TMZ) is an alkylating agent used worldwide for the clinical treatment of GBM; however, the innate and acquired resistance of GBM limits its application. Here, we found that TMZ inhibited the proliferation and induced the G2/M arrest of GBM cells. Therefore, we performed microarrays to identify the cell cycle- and apoptosis-related genes affected by TMZ. Notably, GADD45A was found to be up-regulated by TMZ in both cell cycle and apoptosis arrays. Furthermore, GADD45A knockdown (GADD45Akd) enhanced the cell growth arrest and cell death induced by TMZ, even in natural (T98) and adapted (TR-U373) TMZ-resistant cells. Interestingly, GADD45Akd decreased the expression of O6-methylguanine-DNA methyltransferase (MGMT) in TMZ-resistant cells (T98 and TR-U373). In MGMT-deficient/TMZ-sensitive cells (U87 and U373), GADD45Akd decreased TMZ-induced TP53 expression. Thus, in this study, we investigated the genes influenced by TMZ that were important in GBM therapy, and revealed that GADD45A plays a protective role against TMZ treatment which may through TP53-dependent and MGMT-dependent pathway in TMZ-sensitive and TMZ-resistant GBM, respectively. This protective role of GADD45A against TMZ treatment may provide a new therapeutic strategy for GBM treatment.Hsiao-Han WangTsuey-Yu ChangWei-Chen LinKuo-Chen WeiJyh-Wei ShinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hsiao-Han Wang Tsuey-Yu Chang Wei-Chen Lin Kuo-Chen Wei Jyh-Wei Shin GADD45A plays a protective role against temozolomide treatment in glioblastoma cells
description	Abstract Glioblastoma multiforme (GBM) is one of the most aggressive cancers. Despite recent advances in multimodal therapies, high-grade glioma remains fatal. Temozolomide (TMZ) is an alkylating agent used worldwide for the clinical treatment of GBM; however, the innate and acquired resistance of GBM limits its application. Here, we found that TMZ inhibited the proliferation and induced the G2/M arrest of GBM cells. Therefore, we performed microarrays to identify the cell cycle- and apoptosis-related genes affected by TMZ. Notably, GADD45A was found to be up-regulated by TMZ in both cell cycle and apoptosis arrays. Furthermore, GADD45A knockdown (GADD45Akd) enhanced the cell growth arrest and cell death induced by TMZ, even in natural (T98) and adapted (TR-U373) TMZ-resistant cells. Interestingly, GADD45Akd decreased the expression of O6-methylguanine-DNA methyltransferase (MGMT) in TMZ-resistant cells (T98 and TR-U373). In MGMT-deficient/TMZ-sensitive cells (U87 and U373), GADD45Akd decreased TMZ-induced TP53 expression. Thus, in this study, we investigated the genes influenced by TMZ that were important in GBM therapy, and revealed that GADD45A plays a protective role against TMZ treatment which may through TP53-dependent and MGMT-dependent pathway in TMZ-sensitive and TMZ-resistant GBM, respectively. This protective role of GADD45A against TMZ treatment may provide a new therapeutic strategy for GBM treatment.
format	article
author	Hsiao-Han Wang Tsuey-Yu Chang Wei-Chen Lin Kuo-Chen Wei Jyh-Wei Shin
author_facet	Hsiao-Han Wang Tsuey-Yu Chang Wei-Chen Lin Kuo-Chen Wei Jyh-Wei Shin
author_sort	Hsiao-Han Wang
title	GADD45A plays a protective role against temozolomide treatment in glioblastoma cells
title_short	GADD45A plays a protective role against temozolomide treatment in glioblastoma cells
title_full	GADD45A plays a protective role against temozolomide treatment in glioblastoma cells
title_fullStr	GADD45A plays a protective role against temozolomide treatment in glioblastoma cells
title_full_unstemmed	GADD45A plays a protective role against temozolomide treatment in glioblastoma cells
title_sort	gadd45a plays a protective role against temozolomide treatment in glioblastoma cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/1ee0ffa440bc41b78b22d295136c806d
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GADD45A plays a protective role against temozolomide treatment in glioblastoma cells

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