The cytotoxic effect of copper (II) complexes with halogenated 1,3-disubstituted arylthioureas on cancer and bacterial cells

A series of eight copper (II) complexes with 3-(4-chloro-3-nitrophenyl)thiourea were designed and synthesized. The cytotoxic activity of all compounds was assessed in three human cancer cell lines (SW480, SW620, PC3) and human normal keratinocytes (HaCaT). The complexes 1, 3, 5, 7 and 8 were cytotoxic to the studied tumor cells in the low micromolar range, without affecting the normal cells. The complexes 1, 3, 7 and 8 induced lactate dehydrogenase (LDH) release in all cancer cell lines, but not in the HaCaT cells. They provoked early apoptosis in pathological cells, especially in SW480 and PC3 cells. The ability of compounds 1, 3, 7 and 8 to diminish interleukin-6 (IL-6) concentration in a cell was established. For the first time, the influence of the most promising Cu (II) complexes on intensities of detoxifying and reactive oxygen species (ROS) scavenging the enzymes of tumor cells was studied. The cytotoxic effect of all copper (II) conjugates against standard and hospital bacterial strains was also proved

Physicochemical, structural, and adsorption characteristics of DMSPS-co-DVB nanopolymers

The aim of this work is the synthesis and characterization of the series of S,S′-thiodi-4,1-phenylene bis(thio-methacrylate)-co-divinylbenzene (DMSPS-co-DVB) nanomaterials. The series of new nanopolymers including three mixed systems with different ratios of DMSPS and DVB components, DMSPS-co-DVB = 1:1, DMSPS-co-DVB = 1:2, and DMSPS-co-DVB = 1:3, was synthesized in the polymerization reaction. The research task is to investigate the influence of the reaction mixture composition on morphological, textural, and structural properties of final nanosystems including size, shape, and agglomeration effect. The advanced biphasic nanomaterials enriched with thiol groups were successfully synthesized as potential sorbents for binding organic substances, heavy metals, or biomolecules. To determine the impact of the DMSPS monomer on the final properties of DMSPS-co-DVB nanocomposites, several techniques were applied to reveal the nano-dimensional structure (SAXS), texture (low-temperature nitrogen sorption), general morphology (SEM), acid–base properties (potentiometric titration), and surface chemistry and phase bonding effectiveness (FTIR/ATR spectroscopy). Finally, kinetic studies of aniline sorption on polymeric materials were performed

Structure and reactivity of [RuII(terpy)(N^N)Cl]Cl complexes: consequences for biological applications

The crystal structures of [RuII(terpy)(bipy)Cl]Cl·2H2O and [RuII(terpy)(en)Cl]Cl·3H2O, where terpy = 2,2′:6′,2′′-terpyridine, bipy = 2,2′-bipyridine and en = ethylenediamine, were determined and compared to the structure of the complexes in solution obtained by multi-nuclear NMR spectroscopy in DMSOd-6 as a solvent. In aqueous solution, both chlorido complexes aquate fully to the corresponding aqua complexes, viz. [RuII(terpy)(bipy)(H2O)]2+ and [RuII(terpy)(en)(H2O)]2+, within ca. 2 h and ca. 2 min at 37 °C, respectively. The spontaneous aquation reactions can only be suppressed by chloride concentrations as high as 2 to 4 M, i.e. concentrations much higher than that found in human blood. The corresponding aqua complexes are characterized by pKa values of ca. 10 and 11, respectively, which suggest a more labile coordinated water molecule in the case of the [RuII(terpy)(en)(H2O)]2+ complex. Substitution reactions of the aqua complexes with chloride, cyanide and thiourea show that the [RuII(terpy)(en)(H2O)]2+ complex is 30-60 times more labile than the [RuII(terpy)(bipy)(H2O)]2+ complex at 25 °C. Water exchange reactions for both complexes were studied by 17O-NMR and DFT calculations (B3LYP(CPCM)/def2tzvp//B3LYP/def2svp and ωB97XD(CPCM)/def2tzvp//B3LYP/def2svp). Thermal and pressure activation parameters for the water exchange and ligand substitution reactions support the operation of an associative interchange (Ia) process. The difference in reactivity between these complexes can be accounted for in terms of π-back bonding effects of the terpy and bipy ligands and steric hindrance on the bipy complex. Consequences for eventual biological application of the chlorido complexes are discussed

The effects of 3-year growth hormone treatment and body composition in Polish patients with Silver-Russell syndrome

Introduction: Silver-Russell syndrome (SRS) is characterized by clinical and genetic heterogeneity. SRS is the only disease entity associated with (epi)genetic abnormalities of 2 different chromosomes: 7 and 11. In SRS, the 2 most frequent molecular abnormalities are hypomethylation (loss of methylation) of region H19/IGF2:IG-DMR on chromosome 11p15.5 (11p15 LOM) and maternal uniparental disomy of chromosome 7 (upd(7)mat). Therapy with recombinant human growth hormone (rhGH) is implemented to increase body height in children with SRS. The effect of the administered rhGH on height, weight, body mass index (BMI), body composition, and height velocity in patients with SRS during 3 years of rhGH therapy was analysed. Material and methods: 31 SRS patients (23 with 11p15 LOM, 8 with upd(7)mat) and 16 patients small for gestational age (SGA) as a control group were diagnosed and followed up in The Children’s Memorial Health Institute. Patients were eligible for the 2 Polish rhGH treatment programmes [for patients with SGA or with growth hormone deficiency (GHD)]. Anthropometric parameters were collected in all patients. Body composition using bioelectrical impedance was measured in 13 SRS and 14 SGA patients. Results: Height, weight, and weight for height (SDS) at baseline of rhGH therapy were lower in SRS patients than in the SGA control group: –3.3 ± 1.2 vs. -2.6 ± 06 (p = 0.012), –2.5 vs. -1.9 (p = 0.037), –1.7 vs. –1.1 (p = 0.038), respectively. Height SDS was increased from –3.3 ± 1.2 to –1.8 ± 1.0 and from –2.6 ± 0.6 to –1.3 ± 0.7 in the SRS and SGA groups, respectively. Patients with 11p15 LOM and upd(7)mat achieved similar height, 127.0 ± 15.7 vs. 128.9 ± 21.6 cm, and –2.0 ± 1.3 vs. –1.7 ± 1.0 SDS, respectively. Fat mass percentage decreased in SRS patients from 4.2% to 3.0% (p < 0.05) and in SGA patients from 7.6% to 6.6% (p < 0.05). Conclusions: Growth hormone therapy has a positive influence on the growth of SRS patients. Regardless of molecular abnormality type (11p15 LOM vs. upd(7)mat), height velocity was similar in SRS patients during 3 years of rhGH therapy

Arginase isoenzymes in human cirrhotic liver

Cirrhosis leads to an inability of the liver to perform its biochemical functions. It can also lead to hepatocellular carcinoma in which, as we showed lately, arginase isoenzyme pattern changes. The present work presents our results on arginase isoenzymes and their possible role in liver cirrhosis. The study was performed on tissues obtained during liver transplantation from 60 patients with liver cirrhosis, and on samples of histologically normal liver (control) from 40 patients with benign or colorectal cancer liver metastases removed during surgery, 6-7 cm from the tumor border. Arginase isoenzymes AI (so-called liver-type arginase) and AII (called extrahepatic arginase) were identified by Western blotting and isolated by ion-exchange chromatography. Their expression on mRNA level was studied by RT-PCR. A significant decrease in arginase activity, dependent of the liver clinical stage, was observed in cirrhotic tissue. Arginase AI activity and its mRNA level were significantly decreased in cirrhotic liver, whereas the activity and expression of arginase AII were concurrently raised, as compared to normal liver. Since arginase AI is a key enzyme of the urea cycle, whereas arginase AII most probably takes part in the biosynthesis of ornithine and polyamines, the defective ammonia inactivation and increased collagen biosynthesis observed in cirrhotic liver may be related to the changes in arginase AI and AII levels, respectively

The New Face of a Well-Known Antibiotic: A Review of the Anticancer Activity of Enoxacin and Its Derivatives

Enoxacin as a second-generation synthetic quinolone is known for its antibacterial action; however, in recent years there have been studies focusing on its anticancer potential. Interestingly, it turns out that compared to other fluoroquinolones, enoxacin exhibits uncommon cytotoxic properties. Besides its influence on apoptosis, the cell cycle and cell growth, it exhibits a regulatory action on microRNA biogenesis. It was revealed that the molecular targets of the enoxacin-mediated inhibition of osteoclastogenesis are vacuolar H+-ATPase subunits and the c-Jun N-terminal kinase signaling pathway, causing a decrease in cell invasiveness. Interestingly, the prooxidative nature of the subjected fluoroquinolone enhanced the cytotoxic effect. Crucial for the anticancer activity were the carboxyl group at the third carbon atom, fluorine at the seventh carbon atom and nitrogen at the eighth position of naphyridine. Modifications of the parent drug improved the induction of oxidative stress, cell cycle arrest and the dysregulation of microRNA. The inhibition of V-ATPase–microfilament binding was also observed. Enoxacin strongly affected various cancer but not normal cells, excluding keratinocytes, which suffered from phototoxicity. It seems to be an underestimated anticancer drug with pleiotropic action. Furthermore, its usage as a safe antibiotic with well-known pharmacokinetics and selectivity will enhance the development of anticancer treatment strategies. This review covers articles published within the years 2000–2021, with a strong focus on the recent years (2016–2021). However, some canonical papers published in twentieth century are also mentioned

Exosomes in Angiogenesis and Anti-angiogenic Therapy in Cancers

Angiogenesis is the process through which new blood vessels are formed from pre-existing ones. Exosomes are involved in angiogenesis in cancer progression by transporting numerous pro-angiogenic biomolecules like vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMPs), and microRNAs. Exosomes promote angiogenesis by suppressing expression of factor-inhibiting hypoxia-inducible factor 1 (HIF-1). Uptake of tumor-derived exosomes (TEX) by normal endothelial cells activates angiogenic signaling pathways in endothelial cells and stimulates new vessel formation. TEX-driven cross-talk of mesenchymal stem cells (MSCs) with immune cells blocks their anti-tumor activity. Effective inhibition of tumor angiogenesis may arrest tumor progression. Bevacizumab, a VEGF-specific antibody, was the first antiangiogenic agent to enter the clinic. The most important clinical problem associated with cancer therapy using VEGF- or VEFGR-targeting agents is drug resistance. Combined strategies based on angiogenesis inhibitors and immunotherapy effectively enhances therapies in various cancers, but effective treatment requires further research

The Effect of Fatty Acids on Ciprofloxacin Cytotoxic Activity in Prostate Cancer Cell Lines—Does Lipid Component Enhance Anticancer Ciprofloxacin Potential?

Purpose: To assess cytotoxic effect of ciprofloxacin conjugates with fatty acids on prostate cancer cells (LNCaP and DU-145) with different hormone sensitivity, based on previous promising results from the PC3 cells. Methods: Cytotoxicity were estimated using MTT and LDH tests, whereas its mechanisms were estimated by apoptosis and IL-6 assays. The intensity of proteins involved in lipid metabolism was determined using ML-CS assay. Results: The hormone insensitive DU-145 cells were more vulnerable than the hormone sensitive LNCaP cells. The IC50 values for oleic (4), elaidic (5) and docosahexaenoic acid (8) conjugates were 20.2 µM, 17.8 µM and 16.5 µM, respectively, in DU-145 cells, whereas in LNCaP cells IC50 exceeded 20 µM. The strong conjugate cytotoxicity was confirmed in the LDH test, the highest (70.8%) for compound (5) and 64.2% for compound (8) in DU-145 cells. This effect was weaker for LNCaP cells (around 60%). The cytotoxic effect of unconjugated ciprofloxacin and fatty acids was weaker. The early apoptosis was predominant in LNCaP while in DU-145 cells both early and late apoptosis was induced. The tested conjugates decreased IL-6 release in both cancer cell lines by almost 50%. Proteomic analysis indicated influence of the ciprofloxacin conjugates on lipid metabolic proteins in prostatic cancer. Conclusion: Our findings suggested the cytotoxic potential of ciprofloxacin conjugates with reduction in proteins involved in prostate cancer progress