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Trimebutine Promotes Glioma Cell Apoptosis as a Potential Anti-tumor Agent
Gliomas are the most common primary brain tumors with a usually fatal malignancy. They are associated with a poor prognosis although multiple therapeutic options have been available. Trimebutine is one of the prokinetic agents and it has been mainly used for treatment of disorders of the gastrointes...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6021541/ https://www.ncbi.nlm.nih.gov/pubmed/29977208 http://dx.doi.org/10.3389/fphar.2018.00664 |
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author | Fan, Yi-pu Liu, Pei Xue, Wei-kang Zhao, Wei-jiang Pan, Hong-chao |
author_facet | Fan, Yi-pu Liu, Pei Xue, Wei-kang Zhao, Wei-jiang Pan, Hong-chao |
author_sort | Fan, Yi-pu |
collection | PubMed |
description | Gliomas are the most common primary brain tumors with a usually fatal malignancy. They are associated with a poor prognosis although multiple therapeutic options have been available. Trimebutine is one of the prokinetic agents and it has been mainly used for treatment of disorders of the gastrointestinal (GI) tract such as irritable bowel syndrome. However, its effects on glioma cells remain unknown. Here, we used various concentrations of trimebutine to treat SHG44, U251, and U-87 MG human glioma/glioblastoma cells. And combined experiments of MTT, colony formation assay, and wound healing assay, as well as western blot and immunofluorescence staining were used to evaluate the effects of trimebutine on glioma cells. The results demonstrated that trimebutine significantly inhibited cell viability and colony formation. A significant inhibition of glioma cell migration was also indicated by wound healing assay. In addition, trimebutine promoted cell apoptosis and induced Bcl-2 downregulation, accompanied with Bax upregulation. Both immunofluorescence staining and western blot results showed that trimebutine increased the level of active Caspase-3. Moreover, trimebutine reduced the activation of both AKT and ERK signaling pathways. In subcutaneous U-87 MG cell xenograft tumors in nude mice, trimebutine significantly inhibited tumor growth. More TUNEL-positive apoptotic cells in tumor sections were observed in trimebutine-treated mice when compared to the vehicle control. Reduced Bcl-2 and upregulated Bax, as well as perturbed p-AKT and p-ERK signaling pathways were also observed in trimebutine-treated xenograft tissues. Our combined data indicated that trimebutine may be potentially applied for the clinical management of glioma/glioblastoma. |
format | Online Article Text |
id | pubmed-6021541 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-60215412018-07-05 Trimebutine Promotes Glioma Cell Apoptosis as a Potential Anti-tumor Agent Fan, Yi-pu Liu, Pei Xue, Wei-kang Zhao, Wei-jiang Pan, Hong-chao Front Pharmacol Pharmacology Gliomas are the most common primary brain tumors with a usually fatal malignancy. They are associated with a poor prognosis although multiple therapeutic options have been available. Trimebutine is one of the prokinetic agents and it has been mainly used for treatment of disorders of the gastrointestinal (GI) tract such as irritable bowel syndrome. However, its effects on glioma cells remain unknown. Here, we used various concentrations of trimebutine to treat SHG44, U251, and U-87 MG human glioma/glioblastoma cells. And combined experiments of MTT, colony formation assay, and wound healing assay, as well as western blot and immunofluorescence staining were used to evaluate the effects of trimebutine on glioma cells. The results demonstrated that trimebutine significantly inhibited cell viability and colony formation. A significant inhibition of glioma cell migration was also indicated by wound healing assay. In addition, trimebutine promoted cell apoptosis and induced Bcl-2 downregulation, accompanied with Bax upregulation. Both immunofluorescence staining and western blot results showed that trimebutine increased the level of active Caspase-3. Moreover, trimebutine reduced the activation of both AKT and ERK signaling pathways. In subcutaneous U-87 MG cell xenograft tumors in nude mice, trimebutine significantly inhibited tumor growth. More TUNEL-positive apoptotic cells in tumor sections were observed in trimebutine-treated mice when compared to the vehicle control. Reduced Bcl-2 and upregulated Bax, as well as perturbed p-AKT and p-ERK signaling pathways were also observed in trimebutine-treated xenograft tissues. Our combined data indicated that trimebutine may be potentially applied for the clinical management of glioma/glioblastoma. Frontiers Media S.A. 2018-06-21 /pmc/articles/PMC6021541/ /pubmed/29977208 http://dx.doi.org/10.3389/fphar.2018.00664 Text en Copyright © 2018 Fan, Liu, Xue, Zhao and Pan. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Fan, Yi-pu Liu, Pei Xue, Wei-kang Zhao, Wei-jiang Pan, Hong-chao Trimebutine Promotes Glioma Cell Apoptosis as a Potential Anti-tumor Agent |
title | Trimebutine Promotes Glioma Cell Apoptosis as a Potential Anti-tumor Agent |
title_full | Trimebutine Promotes Glioma Cell Apoptosis as a Potential Anti-tumor Agent |
title_fullStr | Trimebutine Promotes Glioma Cell Apoptosis as a Potential Anti-tumor Agent |
title_full_unstemmed | Trimebutine Promotes Glioma Cell Apoptosis as a Potential Anti-tumor Agent |
title_short | Trimebutine Promotes Glioma Cell Apoptosis as a Potential Anti-tumor Agent |
title_sort | trimebutine promotes glioma cell apoptosis as a potential anti-tumor agent |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6021541/ https://www.ncbi.nlm.nih.gov/pubmed/29977208 http://dx.doi.org/10.3389/fphar.2018.00664 |
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