Application of the antitussive agents oxelaidin and butamirate as anti-glioma agents

Abstract Glioblastoma (GBM) is an aggressive brain tumor with a strong tendency of relapse and resistance to chemotherapy, but we currently lack non-toxic agents that effectively treat GBM. In this study, high-throughput screening of FDA-approved drugs was performed to identify safe and effective mo...

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Autores principales:	Sook-Ja Lee, Seon-Yong Yeom, Jee-Young Lee, Chaehwa Park
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fab0443ab905436e852376e5d9bcec93
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spelling	oai:doaj.org-article:fab0443ab905436e852376e5d9bcec932021-12-02T17:15:32ZApplication of the antitussive agents oxelaidin and butamirate as anti-glioma agents10.1038/s41598-021-89238-92045-2322https://doaj.org/article/fab0443ab905436e852376e5d9bcec932021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89238-9https://doaj.org/toc/2045-2322Abstract Glioblastoma (GBM) is an aggressive brain tumor with a strong tendency of relapse and resistance to chemotherapy, but we currently lack non-toxic agents that effectively treat GBM. In this study, high-throughput screening of FDA-approved drugs was performed to identify safe and effective molecules and test their effect on GBM cell lines, LN229, U87 and T98G. Cough suppressants, oxelaidin and butamirate inhibited GBM growth. A Ras family GTPase, Ras-related associated with diabetes (RRAD), contributes to activation of STAT3, which is essential for survival and growth of many cancer types. Interestingly, oxelaidin and butamirate did not affect proliferation in RRAD negative GBM cells. Docking simulation analyses revealed selective interactions between oxelaidin and RRAD. The mechanism by which butamirate and oxelaidin inhibits GBM cell growth involves the suppression of STAT3 transcriptional activity, leading to down-regulation of cyclin D1 and survivin. In addition, components of RRAD-associated signaling cascades, including p-EGFR, p-Akt, and p-STAT3, were inhibited upon oxelaidin treatment. Intraperitoneal administration of oxelaidin or butamirate markedly suppressed tumor growth in a glioblastoma xenograft mouse model without significant adverse effects. Our collective findings indicate that oxelaidin and butamirate exert anti-tumor effects in glioblastoma, supporting its utility as a novel therapeutic candidate for glioblastoma.Sook-Ja LeeSeon-Yong YeomJee-Young LeeChaehwa ParkNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sook-Ja Lee Seon-Yong Yeom Jee-Young Lee Chaehwa Park Application of the antitussive agents oxelaidin and butamirate as anti-glioma agents
description	Abstract Glioblastoma (GBM) is an aggressive brain tumor with a strong tendency of relapse and resistance to chemotherapy, but we currently lack non-toxic agents that effectively treat GBM. In this study, high-throughput screening of FDA-approved drugs was performed to identify safe and effective molecules and test their effect on GBM cell lines, LN229, U87 and T98G. Cough suppressants, oxelaidin and butamirate inhibited GBM growth. A Ras family GTPase, Ras-related associated with diabetes (RRAD), contributes to activation of STAT3, which is essential for survival and growth of many cancer types. Interestingly, oxelaidin and butamirate did not affect proliferation in RRAD negative GBM cells. Docking simulation analyses revealed selective interactions between oxelaidin and RRAD. The mechanism by which butamirate and oxelaidin inhibits GBM cell growth involves the suppression of STAT3 transcriptional activity, leading to down-regulation of cyclin D1 and survivin. In addition, components of RRAD-associated signaling cascades, including p-EGFR, p-Akt, and p-STAT3, were inhibited upon oxelaidin treatment. Intraperitoneal administration of oxelaidin or butamirate markedly suppressed tumor growth in a glioblastoma xenograft mouse model without significant adverse effects. Our collective findings indicate that oxelaidin and butamirate exert anti-tumor effects in glioblastoma, supporting its utility as a novel therapeutic candidate for glioblastoma.
format	article
author	Sook-Ja Lee Seon-Yong Yeom Jee-Young Lee Chaehwa Park
author_facet	Sook-Ja Lee Seon-Yong Yeom Jee-Young Lee Chaehwa Park
author_sort	Sook-Ja Lee
title	Application of the antitussive agents oxelaidin and butamirate as anti-glioma agents
title_short	Application of the antitussive agents oxelaidin and butamirate as anti-glioma agents
title_full	Application of the antitussive agents oxelaidin and butamirate as anti-glioma agents
title_fullStr	Application of the antitussive agents oxelaidin and butamirate as anti-glioma agents
title_full_unstemmed	Application of the antitussive agents oxelaidin and butamirate as anti-glioma agents
title_sort	application of the antitussive agents oxelaidin and butamirate as anti-glioma agents
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/fab0443ab905436e852376e5d9bcec93
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Application of the antitussive agents oxelaidin and butamirate as anti-glioma agents

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