Induction of Mitosis Delay and Apoptosis by CDDO-TFEA in Glioblastoma Multiforme

Background: Glioblastoma multiforme (GBM) is the vicious malignant brain tumor in adults. Despite advances multi-disciplinary treatment, GBM constinues to have a poor overall survival. CDDO-trifluoroethyl-amide (CDDO-TEFA), a trifluoroethylamidederivative of CDDO, is an Nrf2/ARE pathway activator. C...

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Autores principales:	Tai-Hsin Tsai, Ann-Shung Lieu, Tzuu-Yuan Huang, Aij-Lie Kwan, Chih-Lung Lin, Yi-Chiang Hsu
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	CDDO-TFEA GBM cell cycle RTA 404 apoptosis Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/b598310561bd4451b259cc3b722056fd
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spelling	oai:doaj.org-article:b598310561bd4451b259cc3b722056fd2021-11-08T05:09:24ZInduction of Mitosis Delay and Apoptosis by CDDO-TFEA in Glioblastoma Multiforme1663-981210.3389/fphar.2021.756228https://doaj.org/article/b598310561bd4451b259cc3b722056fd2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.756228/fullhttps://doaj.org/toc/1663-9812Background: Glioblastoma multiforme (GBM) is the vicious malignant brain tumor in adults. Despite advances multi-disciplinary treatment, GBM constinues to have a poor overall survival. CDDO-trifluoroethyl-amide (CDDO-TEFA), a trifluoroethylamidederivative of CDDO, is an Nrf2/ARE pathway activator. CDDO-TEFEA is used to inhibit proliferation and induce apoptosis in glioma cells. However, it not clear what effect it may have on tumorigenesis in GBM.Methods: This in vitro study evaluated the effects of CDDO-TFEA on GBM cells. To do this, we treated GBM8401 cell lines with CDDO-TFEA and assessed apoptosis, cell cycle. DNA content and induction of apoptosis were analyzed by flow cytometry and protein expression by Western blot analysis.Results: CDDO-TFEA significantly inhibited the cell viability and induced cell apoptosis on GBM 8401 cell line. The annexin-FITC/PI assay revealed significant changes in the percentage of apoptotic cells. Treatment with CDDO-TFEA led to a significant reduction in the GBM8401 cells’ mitochondrial membrane potential. A significant rise in the percentage of caspase-3 activity was detected in the treated cells. In addition, treatment with CDDO-TFEA led to an accumulation of G2/M-phase cells. In addition, these results suggest that regarding increased protein synthesis during mitosis in the MPM-2 staining, indicative of a delay in the G2 checkpoint. An analysis of Cyclin B1, CDK1, Cyclin B1/CDK1 complex and CHK1 and CHK2 expression suggested that cell cycle progression seems also to be regulated by CDDO-TFEA. Therefore, CDDO-TFEA may not only induce cell cycle G2/M arrest, it may also exert apoptosis in established GBM cells.Conclusion: CDDO-TFEA can inhibit proliferation, cell cycle progression and induce apoptosis in GBM cells in vitro, possibly though its inhibition of Cyclin B1, CDK1 expression, and Cyclin B1/CDK1 association and the promotion of CHK1 and CHK2 expression.Tai-Hsin TsaiTai-Hsin TsaiTai-Hsin TsaiAnn-Shung LieuAnn-Shung LieuAnn-Shung LieuTzuu-Yuan HuangAij-Lie KwanAij-Lie KwanAij-Lie KwanChih-Lung LinChih-Lung LinChih-Lung LinYi-Chiang HsuFrontiers Media S.A.articleCDDO-TFEAGBMcell cycleRTA 404apoptosisTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	CDDO-TFEA GBM cell cycle RTA 404 apoptosis Therapeutics. Pharmacology RM1-950
spellingShingle	CDDO-TFEA GBM cell cycle RTA 404 apoptosis Therapeutics. Pharmacology RM1-950 Tai-Hsin Tsai Tai-Hsin Tsai Tai-Hsin Tsai Ann-Shung Lieu Ann-Shung Lieu Ann-Shung Lieu Tzuu-Yuan Huang Aij-Lie Kwan Aij-Lie Kwan Aij-Lie Kwan Chih-Lung Lin Chih-Lung Lin Chih-Lung Lin Yi-Chiang Hsu Induction of Mitosis Delay and Apoptosis by CDDO-TFEA in Glioblastoma Multiforme
description	Background: Glioblastoma multiforme (GBM) is the vicious malignant brain tumor in adults. Despite advances multi-disciplinary treatment, GBM constinues to have a poor overall survival. CDDO-trifluoroethyl-amide (CDDO-TEFA), a trifluoroethylamidederivative of CDDO, is an Nrf2/ARE pathway activator. CDDO-TEFEA is used to inhibit proliferation and induce apoptosis in glioma cells. However, it not clear what effect it may have on tumorigenesis in GBM.Methods: This in vitro study evaluated the effects of CDDO-TFEA on GBM cells. To do this, we treated GBM8401 cell lines with CDDO-TFEA and assessed apoptosis, cell cycle. DNA content and induction of apoptosis were analyzed by flow cytometry and protein expression by Western blot analysis.Results: CDDO-TFEA significantly inhibited the cell viability and induced cell apoptosis on GBM 8401 cell line. The annexin-FITC/PI assay revealed significant changes in the percentage of apoptotic cells. Treatment with CDDO-TFEA led to a significant reduction in the GBM8401 cells’ mitochondrial membrane potential. A significant rise in the percentage of caspase-3 activity was detected in the treated cells. In addition, treatment with CDDO-TFEA led to an accumulation of G2/M-phase cells. In addition, these results suggest that regarding increased protein synthesis during mitosis in the MPM-2 staining, indicative of a delay in the G2 checkpoint. An analysis of Cyclin B1, CDK1, Cyclin B1/CDK1 complex and CHK1 and CHK2 expression suggested that cell cycle progression seems also to be regulated by CDDO-TFEA. Therefore, CDDO-TFEA may not only induce cell cycle G2/M arrest, it may also exert apoptosis in established GBM cells.Conclusion: CDDO-TFEA can inhibit proliferation, cell cycle progression and induce apoptosis in GBM cells in vitro, possibly though its inhibition of Cyclin B1, CDK1 expression, and Cyclin B1/CDK1 association and the promotion of CHK1 and CHK2 expression.
format	article
author	Tai-Hsin Tsai Tai-Hsin Tsai Tai-Hsin Tsai Ann-Shung Lieu Ann-Shung Lieu Ann-Shung Lieu Tzuu-Yuan Huang Aij-Lie Kwan Aij-Lie Kwan Aij-Lie Kwan Chih-Lung Lin Chih-Lung Lin Chih-Lung Lin Yi-Chiang Hsu
author_facet	Tai-Hsin Tsai Tai-Hsin Tsai Tai-Hsin Tsai Ann-Shung Lieu Ann-Shung Lieu Ann-Shung Lieu Tzuu-Yuan Huang Aij-Lie Kwan Aij-Lie Kwan Aij-Lie Kwan Chih-Lung Lin Chih-Lung Lin Chih-Lung Lin Yi-Chiang Hsu
author_sort	Tai-Hsin Tsai
title	Induction of Mitosis Delay and Apoptosis by CDDO-TFEA in Glioblastoma Multiforme
title_short	Induction of Mitosis Delay and Apoptosis by CDDO-TFEA in Glioblastoma Multiforme
title_full	Induction of Mitosis Delay and Apoptosis by CDDO-TFEA in Glioblastoma Multiforme
title_fullStr	Induction of Mitosis Delay and Apoptosis by CDDO-TFEA in Glioblastoma Multiforme
title_full_unstemmed	Induction of Mitosis Delay and Apoptosis by CDDO-TFEA in Glioblastoma Multiforme
title_sort	induction of mitosis delay and apoptosis by cddo-tfea in glioblastoma multiforme
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/b598310561bd4451b259cc3b722056fd
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Induction of Mitosis Delay and Apoptosis by CDDO-TFEA in Glioblastoma Multiforme

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