PURPOSE. The aim of this study was to evaluate cytotoxic / antitumor properties of newly synthesized metal [Zn(II), Cu(II), Co(II), Ni(II), Zn(II)/Ag(I), Zn(II)/Au(I)] complexes with various ligands (Schiff bases, non-steroidal anti-inflammatory drugs, bile acids) and to introduce an optimized strategy for such investigations in our research activity.
MATERIALS AND METHODS. Human and animal tumor and non-tumor cells were used as model systems. Short-term (3 – 96h) and long-term (> 2 weeks) experiments were carried out using cytotoxicity assays, cytological / immunocytochemical, biochemical and molecular-biological methods to assess the influence of the compounds on cell viability and proliferation and their ability to induce apoptosis/necrosis and/or autophagy.
RESULTS. The examined metal complexes express cytotoxic activity that is time- and concentration-dependent and are more active than the corresponding ligands tested alone. Zn(II)/Au(I) and Zn(II)/Ag(I) complexes with Salen are found to be the most promising cytotoxic agents being effective also in multidrug resistant cancer cells. Their cytotoxic activity is higher than those of cisplatin, oxaliplatin and epirubicin.
CONCLUSIONS. A complex approach, based on a wide range of cell cultures and methods with different molecular / cellular targets and mechanisms of action was optimized and successfully applied for the assessment of cytotoxicity of new metal complexes.
Background: The accumulation of data on beneficial biological effects of probiotics and their metabolic products favors their potential use in the prevention and treatment of various malaises. Methods: Nine postmetabolites from Lactic acid bacteria (LAB) of human or dairy origin and their antiviral activity were studied using the cytopathic effect inhibition test. The virucidal capacity, their influence on the adsorption stage of Koi herpes virus (KHV) and their preventive role against subsequent viral challenge on intact Common carp brain (CCB) cells were also determined by titration assay. Residual viral infectivity in postmetabolites-treated samples was compared to mock-treated controls and Δlgs were calculated. Results: When administered during KHV replication, the microbial products isolated from Lactiplantibacillus plantarum showed remarkable activity with a selectivity index (SI) between 26.5 and 221.4, as those effects were dependent on the sample-virus incubation time. Postmetabolites from Lactobacillus gasseri and Lactiplantibacillus plantarum also demonstrated significant inhibition of KHV replication with SI of 24 and 16, respectively. The bioactive metabolites isolated from Limosilactobacillus fermentum had a minor effect on the viral replicative cycle. Compounds, produced during the fermentation by lactobacilli, grown on different nutritive media and collected at different time points, significantly inhibited extracellular KHV virions. All investigated postmetabolites remarkably blocked KHV attachment to the host cell (CCB), leading to a drop in viral titers by Δlg = 4.25–5.25, and exerted protective effects on CCB cells before they were subjected to viral infection. Conclusions: Our results open new horizons and promote LAB and their postbiotic products to be used in the prophylaxis and therapy of viral infections.
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