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

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.

Halogenated boroxine increases propensity to apoptosis in leukemia (UT‐7) but not non‐tumor cells in vitro

“…In PBMC, this signal is transmitted but within 72 h it is stabilized possibly by intrinsic anti‐apoptotic mechanism activation without committing cells to apoptosis. This finding is in line with previously observed effects of HB treatment compared with positive apoptosis control treatment in UT‐7 cells using other cytogenetic methods of evaluation [ 17 ]. The observed difference in response between the two cell types might be related to the adaptive response of PBMCs to induced cellular stress, resulting in a transient initiation of the process of apoptosis, without a full commitment [ 28 , 29 ].…”

“…from ROS generation [ 28 ], by activation of inflammation pathways rather than entering apoptosis [ 29 ]. As described previously [ 17 ], similar observations have been reported for non‐tumor control cells in other experiments.…”

“…The transcriptional expression dataset of 84 key genes involved in apoptosis‐related pathways was produced with the RT2 Profiler PCR Array System (Qiagen, Hilden, Germany) as described previously [ 17 ]; validated and used as input to obtain graphical presentations of the differential response of targeted genes between two cell‐types treatments. A heat map of the results of the 0.2 mg·mL −1 treated cells (Fig.…”

“…In this study, we aimed to deeply assess a gene expression dataset obtained earlier in work by Hadzic et al. [ 17 ] to monitor possible specific effects of HB treatment on leukemia (UT‐7) cells. This involved the analysis of associated pathways involved in apoptosis regulation using different bioinformatics methods to compare the response of tumor and non‐tumor cells upon the most efficient HB treatment (0.2 mg·mL −1 ), to gain new insights into its mechanism of action and to assess possible promising further application.…”

In silico prediction suggests inhibitory effect of halogenated boroxine on human catalase and carbonic anhydrase

“…K 2 (B 3 O 3 F 4 OH) is a boron inorganic derivative formed in the reaction of potassium hydrofluoride (KHF 2 ) with boric acid, in a molar ratio of 2:3 [6]. Due to the lack of bioactivity research on halogenated boroxine (HB), a group of authors [7][8][9][10][11][12][13] conducted a study that tested the antiproliferative, cytotoxic, and genotoxic potential of dipotassium-trioxohydroxytetrafluorotriborate K 2 (B 3 O 3 F 4 OH) in human cell cultures. The results obtained by these analyses showed significant inhibitory effects of the tested concentrations of HB on cell growth in carcinoma cell cultures, which confirmed the antitumor potential [7,10,[14][15][16].…”