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Toosendanin Exerts an Anti-Cancer Effect in Glioblastoma by Inducing Estrogen Receptor β- and p53-Mediated Apoptosis

Glioblastoma (GBM) is the most common primary brain tumor with median survival of approximately one year. This dismal poor prognosis is due to resistance to currently available chemotherapeutics; therefore, new cytotoxic agents are urgently needed. In the present study, we reported the cytotoxicity...

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Autores principales: Cao, Liang, Qu, Dingding, Wang, Huan, Zhang, Sha, Jia, Chenming, Shi, Zixuan, Wang, Zongren, Zhang, Jian, Ma, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133924/
https://www.ncbi.nlm.nih.gov/pubmed/27869737
http://dx.doi.org/10.3390/ijms17111928
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author Cao, Liang
Qu, Dingding
Wang, Huan
Zhang, Sha
Jia, Chenming
Shi, Zixuan
Wang, Zongren
Zhang, Jian
Ma, Jing
author_facet Cao, Liang
Qu, Dingding
Wang, Huan
Zhang, Sha
Jia, Chenming
Shi, Zixuan
Wang, Zongren
Zhang, Jian
Ma, Jing
author_sort Cao, Liang
collection PubMed
description Glioblastoma (GBM) is the most common primary brain tumor with median survival of approximately one year. This dismal poor prognosis is due to resistance to currently available chemotherapeutics; therefore, new cytotoxic agents are urgently needed. In the present study, we reported the cytotoxicity of toosendanin (TSN) in the GBM U87 and C6 cell lines in vitro and in vivo. By using the MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay, flow cytometry analysis, and Western blot, we found that TSN inhibited U87 and C6 cell proliferation and induced apoptosis at a concentration as low as 10 nM. Administration of TSN also reduced tumor burden in a xenograft model of athymic nude mice. Pharmacological and molecular studies suggested that estrogen receptor β (ERβ) and p53 were prominent targets for TSN. GBM cell apoptosis induced by TSN was a stepwise biological event involving the upregulation of ERβ and contextual activation of functional p53. Collectively, our study indicates, for the first time, that TSN is a candidate of novel anti-cancer drugs for GBM. Furthermore, ERβ and p53 could act as predictive biomarkers for the sensitivity of cancer to TSN.
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spelling pubmed-51339242016-12-12 Toosendanin Exerts an Anti-Cancer Effect in Glioblastoma by Inducing Estrogen Receptor β- and p53-Mediated Apoptosis Cao, Liang Qu, Dingding Wang, Huan Zhang, Sha Jia, Chenming Shi, Zixuan Wang, Zongren Zhang, Jian Ma, Jing Int J Mol Sci Article Glioblastoma (GBM) is the most common primary brain tumor with median survival of approximately one year. This dismal poor prognosis is due to resistance to currently available chemotherapeutics; therefore, new cytotoxic agents are urgently needed. In the present study, we reported the cytotoxicity of toosendanin (TSN) in the GBM U87 and C6 cell lines in vitro and in vivo. By using the MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay, flow cytometry analysis, and Western blot, we found that TSN inhibited U87 and C6 cell proliferation and induced apoptosis at a concentration as low as 10 nM. Administration of TSN also reduced tumor burden in a xenograft model of athymic nude mice. Pharmacological and molecular studies suggested that estrogen receptor β (ERβ) and p53 were prominent targets for TSN. GBM cell apoptosis induced by TSN was a stepwise biological event involving the upregulation of ERβ and contextual activation of functional p53. Collectively, our study indicates, for the first time, that TSN is a candidate of novel anti-cancer drugs for GBM. Furthermore, ERβ and p53 could act as predictive biomarkers for the sensitivity of cancer to TSN. MDPI 2016-11-18 /pmc/articles/PMC5133924/ /pubmed/27869737 http://dx.doi.org/10.3390/ijms17111928 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cao, Liang
Qu, Dingding
Wang, Huan
Zhang, Sha
Jia, Chenming
Shi, Zixuan
Wang, Zongren
Zhang, Jian
Ma, Jing
Toosendanin Exerts an Anti-Cancer Effect in Glioblastoma by Inducing Estrogen Receptor β- and p53-Mediated Apoptosis
title Toosendanin Exerts an Anti-Cancer Effect in Glioblastoma by Inducing Estrogen Receptor β- and p53-Mediated Apoptosis
title_full Toosendanin Exerts an Anti-Cancer Effect in Glioblastoma by Inducing Estrogen Receptor β- and p53-Mediated Apoptosis
title_fullStr Toosendanin Exerts an Anti-Cancer Effect in Glioblastoma by Inducing Estrogen Receptor β- and p53-Mediated Apoptosis
title_full_unstemmed Toosendanin Exerts an Anti-Cancer Effect in Glioblastoma by Inducing Estrogen Receptor β- and p53-Mediated Apoptosis
title_short Toosendanin Exerts an Anti-Cancer Effect in Glioblastoma by Inducing Estrogen Receptor β- and p53-Mediated Apoptosis
title_sort toosendanin exerts an anti-cancer effect in glioblastoma by inducing estrogen receptor β- and p53-mediated apoptosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133924/
https://www.ncbi.nlm.nih.gov/pubmed/27869737
http://dx.doi.org/10.3390/ijms17111928
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