Biochemical and histomorphological findings in Swiss Wistar rats treated with potential boron-containing therapeutic - K2[B3O3F4OH]

Haverić, Anja; Durmić-Pašić, Adaleta; Alić, Amer; Mujezinović, Indira; Smajlović, Ahmed; Ostojić, Jelena; Ahatović, Anesa; Hadžić, Maida; Prašović, Senad; Haverić, Sanin; Galić, Borivoj

doi:10.1016/j.jtemb.2020.126642

Cited by 7 publications

(4 citation statements)

References 30 publications

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Section: Introductionmentioning

confidence: 99%

“…[27] Recent biochemical findings and histomorphological tissue examinations in rats revealed no adverse effects of HB either after the administration of a single dose lower than 35 mg/kg or following repeated administration at 10 mg/kg. [28] However, the proapoptotic activity of HB regarding its action in tumor cells, neither the effects on any type of hematological malignancies have not been known. Accordingly, the aim of this study was to evaluate the anti-leukemic effects of HB based on apoptotic events at cellular and molecular levels to provide new insight into HB's underlying mechanism of action.…”

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confidence: 99%

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

Hadžić

Pojskić

Lojo-Kadric

et al. 2022

J Biochem & Molecular Tox

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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.

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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

Hadžić

Pojskić

Lojo-Kadric

et al. 2022

J Biochem & Molecular Tox

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“…Temporary mild to moderate HB dose-dependent lesions were observed in the kidneys and livers or Wistar rats after single intraperitoneal doses of HB in 25, 35 and 45 mg/kg/body weight (bw) in comparison with control and 10 mg/kg/bw treatment. Adverse effects were not detected in a single dose administration lower than 35 mg/kg or in repeated, nine-days, dosages with 10 mg/kg/bw (Haverić et al 2020).…”

Section: Introductionmentioning

confidence: 90%

Halogenated Boroxine K2 (B3O3F4 Oh) Modulates Metabolic Phenotype and Autophagy in Human Bladder Carcinoma 5637 Cell Line

Elez-Burnjaković

Pojskić

Haverić

et al. 2022

Preprint

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Halogenated boroxine K2(B3O3F4OH), (HB) has effectively inhibited growth of several carcinoma cell lines. Because of the growing interest in autophagy induction as therapeutic approach in bladder carcinoma (BC), we aimed to assess the effects of HB on metabolic phenotype and autophagy levels in 5637 human bladder carcinoma cells (BC). Cytotoxicity was evaluated using alamar blue assay, and degree of autophagy was determined microscopically. Mitochondrial respiration and glycolysis were measured simultaneously. The relative expression of autophagy related genes BECN1, P62, BCL-2, and DRAM1 were determined by real time PCR. HB inhibited cell growth in concentration dependent manner. Starvation significantly increased level of autophagy in positive control compared to the basal level of autophagy in negative control. In HB treated cultures, the degree of autophagy was higher compared to the basal level and metabolic phenotype altered: both glycolysis and oxidative phosphorylation (OXPHOS) were decreased by HB at 0.2 and 0.4 mg/ml. Genes expression was deregulated towards autophagy induction and expansion. These findings suggest that HB disrupts the bioenergetic metabolism, and reduces intracellular survival potential of BC cells. Further molecular studies are needed to confirm and potentially apply these findings.

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“…Temporary mild-to-moderate HB dose-dependent lesions were observed in the kidneys and livers of Wistar rats after single intraperitoneal doses of HB at 25, 35, and 45 mg/kg/body weight (bw) in comparison with the control and 10 mg/kg/bw treatments. Adverse effects were not detected in a single-dose administration lower than 35 mg/kg or in repeated, nine-day dosages with 10 mg/kg/bw [ 33 ]. The median lethal dose (LD50) of HB in Sprague Dawley and Wistar rats and BALB/c mice ranges from 63 to 75 mg/kg, meaning that HB shows moderate toxicity [ 34 ].…”

Section: Introductionmentioning

confidence: 99%

Halogenated Boroxine K2[B3O3F4OH] Modulates Metabolic Phenotype and Autophagy in Human Bladder Carcinoma 5637 Cell Line

Elez-Burnjaković,

Pojskić,

Haverić

et al. 2024

Molecules

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Halogenated boroxine K2[B3O3F4OH] (HB), an inorganic derivative of cyclic anhydride of boronic acid, is patented as a boron-containing compound with potential for the treatment of both benign and malignant skin changes. HB has effectively inhibited the growth of several carcinoma cell lines. Because of the growing interest in autophagy induction as a therapeutic approach in bladder carcinoma (BC), we aimed to assess the effects of HB on metabolic phenotype and autophagy levels in 5637 human bladder carcinoma cells (BC). Cytotoxicity was evaluated using the alamar blue assay, and the degree of autophagy was determined microscopically. Mitochondrial respiration and glycolysis were measured simultaneously. The relative expression of autophagy-related genes BECN1, P62, BCL-2, and DRAM1 was determined by real-time PCR. HB affected cell growth, while starvation significantly increased the level of autophagy in the positive control compared to the basal level of autophagy in the untreated negative control. In HB-treated cultures, the degree of autophagy was higher compared to the basal level, and metabolic phenotypes were altered; both glycolysis and oxidative phosphorylation (OXPHOS) were decreased by HB at 0.2 and 0.4 mg/mL. Gene expression was deregulated towards autophagy induction and expansion. In conclusion, HB disrupted the bioenergetic metabolism and reduced the intracellular survival potential of BC cells. Further molecular studies are needed to confirm these findings and investigate their applicative potential.

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Biochemical and histomorphological findings in Swiss Wistar rats treated with potential boron-containing therapeutic - K2[B3O3F4OH]

Cited by 7 publications

References 30 publications

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

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

Halogenated Boroxine K2 (B3O3F4 Oh) Modulates Metabolic Phenotype and Autophagy in Human Bladder Carcinoma 5637 Cell Line

Halogenated Boroxine K2[B3O3F4OH] Modulates Metabolic Phenotype and Autophagy in Human Bladder Carcinoma 5637 Cell Line

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