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Abnormal activity of the core cell-cycle machinery is seen in essentially all tumor types and represents a driving force of tumorigenesis. Recent studies revealed that cell-cycle proteins regulate a wide range of cellular functions, in addition to promoting cell division. With the clinical success of CDK4/6 inhibitors, it is becoming increasingly clear that targeting individual cell-cycle components may represent an effective anti-cancer strategy. Here, we discuss the potential of inhibiting different cell-cycle proteins for cancer therapy. [ABSTRACT FROM AUTHOR]

Abstract In the present study, two binuclear copper(II) coordination compounds bridged by hydroxy- and thiodipropionic acid have been synthesized. The structure of compounds was determined by X-ray crystallography. The central copper atoms exist in square pyramidal surroundings. Basal plane is formed by nitrogen atoms of amines and oxygen atoms of bridges, whereas apical positions are occupied by oxygen atoms of coordinated water molecules. Temperature dependence study of magnetic susceptibility proved strong antiferromagnetic exchange between copper atoms in hydroxy-bridged complex. These coordination compounds were also tested for their biological activities in vitro. Both coordination compounds exhibit pronounced cytocompatibility in mammalian epithelial cells with no induction of oxidative stress and DNA fragmentation. Moreover, synthesized compounds are hemocompatible and do not alter expression of a marker of multiple cellular stress, p53. On the other hand, both compounds had stimulatory effect on expression of metallothioneins (MT-1/2 and MT-3). Antimicrobial testing on Escherichia coli , Staphylococcus aureus and methicillin-resistant Staphylococcus aureus revealed that both copper compounds exhibit antibacterial activity regardless the cell wall composition. Overall, current work presents a synthesis of Cu(II) coordination compounds with interesting biological behavior and with a promising potential to be further tested in pre-clinical models. Graphical abstract The study describes synthesis and detailed physico-chemical characterization (X-ray, EPR, magnetochemistry) of two binuclear copper(II) coordination compounds with exceptional biocompatibility in mammalian cells and marked antimicrobial activity proved in both, G(+) and G(−) bacterial strains. Unlabelled Image Highlights • Binuclear copper(II) coordination compounds were synthesized and characterized. • Compound with two hydroxo bridges exhibits strong antiferromagnetic properties. • Compounds are biocompatible for mammalian epithelial and red blood cells. • Both compounds exhibit marked antimicrobial properties. [ABSTRACT FROM AUTHOR]

The nanotechnological concept is based on size-dependent properties of particles in the 1–100 nm range. Nevertheless, the connection between their size and effect is still not clear. Thus, we focused on reductive colloidal synthesis, characterization and biological testing of Pt nanoparticles (PtNPs) capped with biocompatible polymer polyvinylpyrrolidone (PVP). Synthesized PtNPs were of 3 different primary sizes (approx. ∼10; ∼14 and > 20 nm) and demonstrated exceptional haemocompatibility. In vitro treatment of three different types of malignant cells (prostate – LNCaP, breast – MDA-MB-231 and neuroblastoma – GI-ME-N) revealed that even marginal differences in PtNPs diameter resulted in changes in their cytotoxicity. The highest cytotoxicity was observed using the smallest PtNPs-10, where 24IC 50 was lower (3.1–6.2 μg/mL) than for cisplatin (8.1–19.8 μg/mL). In contrast to MDA-MB-231 and LNCaP cells, in GI-ME-N cells PtNPs caused noticeable changes in their cellular structure without influencing their viability. Post-exposure analyses revealed that PtNPs-29 and PtNPs-40 were capable of forming considerably higher amount of reactive oxygen species with consequent stimulation of expression of metallothionein (MT1/2 and MT3), at both mRNA and protein level. Overall, our pilot study demonstrates that in the nanoscaled world even the smallest differences can have crucial biological effect. [ABSTRACT FROM AUTHOR]

• Biphasic (anatase-brookite) TiO 2 NPs were synthesized and tested. • Anatase-prevailing TiO 2 NPs induced more oxidative stress and DNA fragmentation. • Anatase-prevailing TiO 2 NPs deregulated proteome of benign epithelial cells. • Anatase crystalline phase contributes to overall cytotoxicity more than brookite. Nanoparticular form of titanium dioxide (TiO 2 NPs) belongs to important industrial material. Despite being widely used, serious contradictions regarding biosafety of TiO 2 NPs remain. We anticipate that such discrepancies could be due to a lack of understanding of a linkage between TiO 2 NPs phase composition and cytotoxicity. Therefore, we synthesized two types of biphasic TiO 2 NPs differing in an anatase-brookite phase composition. The study presents an array of in vitro data suggesting that TiO 2 NPs with a prevailing anatase phase composition possess higher cytotoxicity compared to TiO 2 NPs with an equal anatase-brookite crystallinity. This phenomenon was evidenced by significantly higher inhibition of metabolic activity and growth of epithelial and neuroblast-like cells. Moreover, anatase-prevailing TiO 2 NPs tend to produce higher amount of reactive oxygen species resulting in DNA fragmentation. Further insights into the molecular aspects of cytotoxicity of anatase-prevailing TiO 2 NPs were obtained by comparative proteomics delineating that TiO 2 NPs deregulate expression of a variety of proteins and associated pathways. This inevitably results in a decreased cellular ability to detoxify reactive oxygen species and respond to various stress conditions. The study provides novel data that add another piece to the jigsaw of the relation between structural features of NPs and biosafety. [ABSTRACT FROM AUTHOR]