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新型含硼化合物卤代硼恶嗪通过触发UT-7白血病细胞凋亡诱导选择性细胞毒性。

Novel boron-containing compound, halogenated boroxine, induces selective cytotoxicity through apoptosis triggering in UT-7 leukemia.

作者信息

Hadzic Maida, Pojskic Lejla, Lojo-Kadric Naida, Haveric Anja, Ramic Jasmin, Galic Borivoj, Haveric Sanin

机构信息

Institute for Genetic Engineering and Biotechnology, University of Sarajevo, Sarajevo, Bosnia and Herzegovina.

Faculty of Science, Department of Chemistry, University of Sarajevo, Sarajevo, Bosnia and Herzegovina.

出版信息

J Biochem Mol Toxicol. 2022 May;36(5):e23005. doi: 10.1002/jbt.23005. Epub 2022 Feb 17.

Abstract

Apoptosis induction is a promising approach in targeting tumor cells. As halogenated boroxine (HB) shows antitumor activity, but its mechanism of action in hematological tumors remains unclear, in this study, we aimed to analyze apoptosis triggering in normal and UT-7 leukemia cells by HB. Methods for assessing cell viability and cytotoxicity, apoptosis detection, relative expression of 84 apoptosis-associated genes and BCL-2, and functional analysis were applied. Pronounced HB activities in inhibition of cell viability, cytotoxicity, and apoptosis induction with measurable differences between tumor and normal cells were found. HB modulated the expression of 21 genes, predominantly downregulated the antiapoptotic genes in leukemia. The functional association revealed HB's impact on inhibition of NF-κB signaling pathway. BCL-2 expression decreasing was found only in UT-7 leukemia. This study identified HB as an apoptosis inducer affecting leukemia but not normal cells considering mechanisms of selective activity that may be a great advantage of HB applications.

摘要

诱导凋亡是一种靶向肿瘤细胞的有前景的方法。由于卤代硼恶嗪(HB)具有抗肿瘤活性,但其在血液肿瘤中的作用机制仍不清楚,在本研究中,我们旨在分析HB对正常细胞和UT-7白血病细胞凋亡的触发作用。应用了评估细胞活力和细胞毒性的方法、凋亡检测、84个凋亡相关基因和BCL-2的相对表达以及功能分析。发现HB在抑制细胞活力、细胞毒性和诱导凋亡方面具有显著活性,肿瘤细胞和正常细胞之间存在可测量的差异。HB调节了21个基因的表达,主要下调了白血病中的抗凋亡基因。功能关联揭示了HB对抑制NF-κB信号通路的影响。仅在UT-7白血病中发现BCL-2表达降低。考虑到选择性活性机制,本研究确定HB是一种影响白血病细胞而非正常细胞的凋亡诱导剂,这可能是HB应用的一大优势。

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