Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Buyandelger, Batsaikhan, Bar, Eli E, Hung, Kuo-Sheng, Chen, Ruei-Ming, Chiang, Yung-Hsiao, Liou, Jing-Ping, Huang, Huei-Mei, Wang, Jia-Yi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2020
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
_version_ 1783606721796636672
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
work_keys_str_mv AT buyandelgerbatsaikhan histonedeacetylaseinhibitormpt0b291suppressesgliomagrowthinvitroandinvivopartiallythroughacetylationofp53
AT barelie histonedeacetylaseinhibitormpt0b291suppressesgliomagrowthinvitroandinvivopartiallythroughacetylationofp53
AT hungkuosheng histonedeacetylaseinhibitormpt0b291suppressesgliomagrowthinvitroandinvivopartiallythroughacetylationofp53
AT chenrueiming histonedeacetylaseinhibitormpt0b291suppressesgliomagrowthinvitroandinvivopartiallythroughacetylationofp53
AT chiangyunghsiao histonedeacetylaseinhibitormpt0b291suppressesgliomagrowthinvitroandinvivopartiallythroughacetylationofp53
AT lioujingping histonedeacetylaseinhibitormpt0b291suppressesgliomagrowthinvitroandinvivopartiallythroughacetylationofp53
AT huanghueimei histonedeacetylaseinhibitormpt0b291suppressesgliomagrowthinvitroandinvivopartiallythroughacetylationofp53
AT wangjiayi histonedeacetylaseinhibitormpt0b291suppressesgliomagrowthinvitroandinvivopartiallythroughacetylationofp53