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Histone deacetylase inhibitor MPT0B291 suppresses Glioma Growth in vitro and in vivo partially through acetylation of p53
Background: Histone deacetylase (HDAC) inhibitors have emerged as a new class of anti-tumor agents for various types of tumors, including glioblastoma. Methods and results: We found that a novel HDAC inhibitor, MPT0B291, significantly reduced the cell viability and increased cell death of human and...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Ivyspring International Publisher
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645997/ https://www.ncbi.nlm.nih.gov/pubmed/33162824 http://dx.doi.org/10.7150/ijbs.45505 |
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author | Buyandelger, Batsaikhan Bar, Eli E Hung, Kuo-Sheng Chen, Ruei-Ming Chiang, Yung-Hsiao Liou, Jing-Ping Huang, Huei-Mei Wang, Jia-Yi |
author_facet | Buyandelger, Batsaikhan Bar, Eli E Hung, Kuo-Sheng Chen, Ruei-Ming Chiang, Yung-Hsiao Liou, Jing-Ping Huang, Huei-Mei Wang, Jia-Yi |
author_sort | Buyandelger, Batsaikhan |
collection | PubMed |
description | Background: Histone deacetylase (HDAC) inhibitors have emerged as a new class of anti-tumor agents for various types of tumors, including glioblastoma. Methods and results: We found that a novel HDAC inhibitor, MPT0B291, significantly reduced the cell viability and increased cell death of human and rat glioma cell lines, but not in normal astrocytes. We also demonstrated that MPT0B291 suppressed proliferation by inducing G1 phase cell cycle arrest and increased apoptosis in human and rat glioma cell lines by flow cytometry and immunocytochemistry. We further investigated the anti-tumor effects of MPT0B291 in xenograft (mouse) and allograft (rat) models. The IVIS200 images and histological analysis indicated MPT0B291 (25 mg/kg, p. o.) reduced tumor volume. Mechanistically, MPT0B291 increased phosphorylation and acetylation/activation of p53 and increased mRNA levels of the apoptosis related genes PUMA, Bax, and Apaf1 as well as increased protein level of PUMA, Apaf1 in C6 cell line. The expression of cell cycle related gene p21 was also increased and Cdk2, Cdk4 were decreased by MPT0B291. Conclusion: Our study highlights the anti-tumor efficacy of a novel compound MPT0B291 on glioma growth. |
format | Online Article Text |
id | pubmed-7645997 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-76459972020-11-06 Histone deacetylase inhibitor MPT0B291 suppresses Glioma Growth in vitro and in vivo partially through acetylation of p53 Buyandelger, Batsaikhan Bar, Eli E Hung, Kuo-Sheng Chen, Ruei-Ming Chiang, Yung-Hsiao Liou, Jing-Ping Huang, Huei-Mei Wang, Jia-Yi Int J Biol Sci Research Paper Background: Histone deacetylase (HDAC) inhibitors have emerged as a new class of anti-tumor agents for various types of tumors, including glioblastoma. Methods and results: We found that a novel HDAC inhibitor, MPT0B291, significantly reduced the cell viability and increased cell death of human and rat glioma cell lines, but not in normal astrocytes. We also demonstrated that MPT0B291 suppressed proliferation by inducing G1 phase cell cycle arrest and increased apoptosis in human and rat glioma cell lines by flow cytometry and immunocytochemistry. We further investigated the anti-tumor effects of MPT0B291 in xenograft (mouse) and allograft (rat) models. The IVIS200 images and histological analysis indicated MPT0B291 (25 mg/kg, p. o.) reduced tumor volume. Mechanistically, MPT0B291 increased phosphorylation and acetylation/activation of p53 and increased mRNA levels of the apoptosis related genes PUMA, Bax, and Apaf1 as well as increased protein level of PUMA, Apaf1 in C6 cell line. The expression of cell cycle related gene p21 was also increased and Cdk2, Cdk4 were decreased by MPT0B291. Conclusion: Our study highlights the anti-tumor efficacy of a novel compound MPT0B291 on glioma growth. Ivyspring International Publisher 2020-10-19 /pmc/articles/PMC7645997/ /pubmed/33162824 http://dx.doi.org/10.7150/ijbs.45505 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Buyandelger, Batsaikhan Bar, Eli E Hung, Kuo-Sheng Chen, Ruei-Ming Chiang, Yung-Hsiao Liou, Jing-Ping Huang, Huei-Mei Wang, Jia-Yi Histone deacetylase inhibitor MPT0B291 suppresses Glioma Growth in vitro and in vivo partially through acetylation of p53 |
title | Histone deacetylase inhibitor MPT0B291 suppresses Glioma Growth in vitro and in vivo partially through acetylation of p53 |
title_full | Histone deacetylase inhibitor MPT0B291 suppresses Glioma Growth in vitro and in vivo partially through acetylation of p53 |
title_fullStr | Histone deacetylase inhibitor MPT0B291 suppresses Glioma Growth in vitro and in vivo partially through acetylation of p53 |
title_full_unstemmed | Histone deacetylase inhibitor MPT0B291 suppresses Glioma Growth in vitro and in vivo partially through acetylation of p53 |
title_short | Histone deacetylase inhibitor MPT0B291 suppresses Glioma Growth in vitro and in vivo partially through acetylation of p53 |
title_sort | histone deacetylase inhibitor mpt0b291 suppresses glioma growth in vitro and in vivo partially through acetylation of p53 |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645997/ https://www.ncbi.nlm.nih.gov/pubmed/33162824 http://dx.doi.org/10.7150/ijbs.45505 |
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