Histone Deacetylase Inhibitor MPT0B291 Suppresses Glioma Growth and Partially Through Acetylation of P53

Overview

Journal Int J Biol Sci

Specialty Biology

Date 2020 Nov 9

PMID 33162824

Citations 16

Authors

Batsaikhan Buyandelger

Eli E Bar

Kuo-Sheng Hung

Ruei-Ming Chen

Yung-Hsiao Chiang

Jing-Ping Liou

Huei-Mei Huang

Jia-Yi Wang

Affiliations

Soon will be listed here.

Abstract

Histone deacetylase (HDAC) inhibitors have emerged as a new class of anti-tumor agents for various types of tumors, including glioblastoma. 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, ) 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. Our study highlights the anti-tumor efficacy of a novel compound MPT0B291 on glioma growth.

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