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Int. J. Mol. Sci. 2016, 17(11), 1928; doi:10.3390/ijms17111928

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

1
Department of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China
2
Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi’an 710032, China
3
Department of Acupuncture, Shaanxi Hospital of Traditional Chinese Medicine, Xi’an 710032, China
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Academic Editor: Ge Zhang
Received: 12 October 2016 / Revised: 9 November 2016 / Accepted: 10 November 2016 / Published: 18 November 2016
(This article belongs to the Special Issue Translational Molecular Medicine & Molecular Drug Discovery)
View Full-Text   |   Download PDF [3499 KB, uploaded 18 November 2016]   |  

Abstract

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. View Full-Text
Keywords: glioblastoma; toosendanin; apoptosis; estrogen receptor β; p53 glioblastoma; toosendanin; apoptosis; estrogen receptor β; p53
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Cao, L.; Qu, D.; Wang, H.; Zhang, S.; Jia, C.; Shi, Z.; Wang, Z.; Zhang, J.; Ma, J. Toosendanin Exerts an Anti-Cancer Effect in Glioblastoma by Inducing Estrogen Receptor β- and p53-Mediated Apoptosis. Int. J. Mol. Sci. 2016, 17, 1928.

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