Histone deacetylase inhibitor MPT0B291 suppresses glioma growth in vitro and in vivo partially through acetylation of p53

研究成果: 雜誌貢獻文章同行評審

摘要

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.
原文英語
頁(從 - 到)3184-3199
頁數16
期刊International Journal of Biological Sciences
16
發行號16
DOIs
出版狀態已發佈 - 2020

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Developmental Biology
  • Cell Biology

指紋 深入研究「Histone deacetylase inhibitor MPT0B291 suppresses glioma growth in vitro and in vivo partially through acetylation of p53」主題。共同形成了獨特的指紋。

引用此