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

中文翻译：

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组蛋白去乙酰化酶抑制剂 MPT0B291 部分通过 p53 的乙酰化抑制体外和体内胶质瘤的生长

背景：组蛋白去乙酰化酶 (HDAC) 抑制剂已成为治疗各种类型肿瘤（包括胶质母细胞瘤）的新型抗肿瘤药物。/n方法和结果：我们发现一种新型 HDAC 抑制剂 MPT0B291 显着降低了细胞活力和增加人和大鼠神经胶质瘤细胞系的细胞死亡，但在正常星形胶质细胞中没有。我们还通过流式细胞术和免疫细胞化学证明 MPT0B291 通过诱导 G1 期细胞周期停滞和增加人和大鼠神经胶质瘤细胞系的细胞凋亡来抑制增殖。我们进一步研究了 MPT0B291 在异种移植（小鼠）和同种异体移植（大鼠）模型中的抗肿瘤作用。IVIS200 图像和组织学分析表明 MPT0B291 (25 mg/kg, po) 减少肿瘤体积。从机制上讲，MPT0B291 增加了 p53 的磷酸化和乙酰化/活化，增加了凋亡相关基因 PUMA、Bax 和 Apaf1 的 mRNA 水平，以及增加了 C6 细胞系中 PUMA、Apaf1 的蛋白质水平。MPT0B291./n 还增加了细胞周期相关基因 p21 的表达，降低了 Cdk2、Cdk4。/n结论：我们的研究强调了新型化合物 MPT0B291 对神经胶质瘤生长的抗肿瘤功效。