No abstract

We have examined antiproliferative, cytotoxic, and genotoxic potential of a halogenated boroxine dipotassium trioxohydroxytetrafluorotriborate (K₂[B₃O₃F₄OH]). The impact on cell growth was evaluated by alamarBlue assay in basal cell carcinoma culture. Cytostatic, cytotoxic, and genotoxic potential were evaluated in lymphocytes culture, applying cytokinesis-block micronucleus cytome assay and chromosome aberrations analysis. Tested concentrations (0.05, 0.1, 0.2, and 0.4 mg/mL) were correlated with inhibition of cell growth in basal cell carcinoma culture and with the lymphocytes proliferation. Clastogenic activity has been confirmed, without evidences of aneugenic activity, in human lymphocytes.

Cytogenetic biomarkers, such as micronuclei in peripheral blood or oral mucosa, are widely used for evaluation of exposure to genotoxins or carcinogens. Tobacco is one of the strongest carcinogens, responsible for development of different types of cancers. The aim of this study was to assess the genotoxicity of cigarette consumption in young smokers and to correlate results of cytogenetic analysis in peripheral blood lymphocytes and exfoliated buccal cells. The study was conducted on samples taken from 43 smokers and 44 non-smokers, young individuals from Bosnia and Herzegovina. Significantly higher frequency of micronuclei in peripheral blood lymphocytes was observed in smokers (p < 0.05). No significant correlations were found for age, duration and intensity of smoking, and frequency of micronuclei in lymphocytes. Significantly higher frequency of degenerated (apoptotic) buccal cells was also revealed in smokers (p < 0.05). The frequency of apoptotic cells in smokers was significantly influenced by the age of participants (F = 8.649; p < 0.01) and duration of smoking (F = 5.389; p < 0.05). Results of cytogenetic analysis conducted in peripheral blood and exfoliated buccal cells are in significant positive correlation, indicating complementarities of those analyses.

Recently it was found that dipotassium-trioxohydroxytetrafluorotriborate, K2(B3O3F4OH), is a potent and highly specific inhibitor of precancerous cell processes. We conducted gene expression profiling of human melanoma cells before and after treatment with two concentrations (0.1 and 1 mM) of this boron inorganic derivative in order to assess its effects on deregulation of genes associated with tumor pathways. Parallel trypan blue exclusion assay was performed to assess the cytotoxicity effects of this chemical. Treatment with K2(B3O3F4OH) induced a significant decrease of cell viability in melanoma cellline at both tested concentrations. Furthermore, these treatments caused deregulation of more than 30 genes known as common anti-tumor drug targets. IGF-1 and hTERT were found to be significantly downregulated and this result may imply potential use of K2(B3O3F4OH) as an inhibitor or human telomerase and insulin-like growth factor 1, both of which are associated with various tumor pathways.

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.

This study was undertaken in order to evaluate possible antioxidative and antiproliferative activities of three Helleborus taxa. The dry leaves and roots of three Helleborus taxa were extracted with ethanol and water. A phytochemical evaluation of the selected extracts was performed using spectrophotometric methods and a 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity assay was used for measuring the antioxidative activity of extracts. The antiproliferative activity of the three Helleborus taxa was studied using Burkitt's lymphoma B cells (BJAB) cell lines. The phytochemical evaluation showed that the leaves contain high levels of total phenolic and flavonoid content. Results from the DPPH assay indicated that the activity of the ethanol and water extracts of the leaves was higher than that of positive control (thymol). Extracts from the roots of H. odorus also displayed higher antioxidant activity than the positive probe, while H. mulifidus and H. hercegovinus root extracts were less effective. A statistically significant correlation between total phenolic content and antioxidative properties indicates that these compounds contribute to the antioxidant activity. The highest percentage of cell growth inhibition was observed when testing the water root extracts of H. multifidus (50.14%) and H. hercegovinus (49.04%). In contrast, the water leaf extract of H. hercegovinus exhibited the lowest inhibition of cell growth (8.59%), although it showed strong antioxidant activity.

Plant bioflavonoids are widely present in the human diet and have various protective properties. In this study, we have demonstrated the capacity of delphinidin and luteolin to increase human telomerase reverse transcriptase (hTERT) expression level and act as protective agents against halogenated boroxine-induced genotoxic damage. Halogenated boroxine K2(B3O3F4OH) (HB), is a novel compound with potential for the treatment of both benign and malignant skin changes. In vivo and in vitro studies have confirmed the inhibitory effects of HB on carcinoma cell proliferation and cell cycle progression as well as enzyme inhibition. However, minor genotoxic effects of HB are registered in higher applied concentrations, but those can be suppressed by in vitro addition of delphinidin and luteolin in appropriate concentrations. Fresh peripheral blood samples were cultivated for 72 h followed by independent and concomitant treatments of HB with luteolin or delphinidin. We analyzed the differences in relative hTERT expression between series of treatments compared with controls, which were based on normalized ratios with housekeeping genes. The obtained results have shown that selected bioflavonoids induce upregulation of hTERT that may contribute to the repair of genotoxic damage in vitro.

Due to the exposure to various potentially genotoxic xenobiotics, derived from recent war activities such as NATO air strikes with antitank ammunition containing depleted uranium, we have evaluated chromosome aberrations in 84 peripheral blood samples from three local populations. One population sample included 30 individuals who lived in the Sarajevo area during and after the war (exposed to potential genotoxins), second population was presented with 26 employees of the tank repair facility in Hadzići (target of NATO air strikes), and 28 inhabitants of Posusje (not exposed to war-related activities) were treated as sample of control population. The mean of chromosome aberration frequencies for the population from Hadzići was significantly higher than the frequencies for the two other populations. Point bi-serial coefficient analysis did not reveal any relationship between the frequencies of chromosome aberrations and smoking habits or gender. Results suggest that depleted uranium could be a risk factor for human health.