Oxidative Properties of Polystyrene Nanoparticles with Different Diameters in Human Peripheral Blood Mononuclear Cells (In Vitro Study)

With the ongoing commercialization, human exposure to plastic nanoparticles will dramatically increase, and evaluation of their potential toxicity is essential. There is an ongoing discussion on the human health effects induced by plastic particles. For this reason, in our work, we assessed the effect of polystyrene nanoparticles (PS-NPs) of various diameters (29, 44 and 72 nm) on selected parameters of oxidative stress and the viability of human peripheral blood mononuclear cells (PBMCs) in the in vitro system. Cells were incubated with PS-NPs for 24 h in the concentration range of 0.001 to 100 µg/mL and then labeled: formation of reactive oxygen species (ROS) (including hydroxyl radical), protein and lipid oxidation and cell viability. We showed that PS-NPs disturbed the redox balance in PBMCs. They increased ROS levels and induced lipid and protein oxidation, and, finally, the tested nanoparticles induced a decrease in PBMCs viability. The earliest changes in the PBMCs were observed in cells incubated with the smallest PS-NPs, at a concentration of 0.01 μg/mL. A comparison of the action of the studied nanoparticles showed that PS-NPs (29 nm) exhibited a stronger oxidative potential in PBMCs. We concluded that the toxicity and oxidative properties of the PS-NPs examined depended to significant degree on their diameter

Anticancer Activity of the Acetylenic Derivative of Betulin Phosphate Involves Induction of Necrotic-Like Death in Breast Cancer Cells In Vitro

Betulin (BT) is a natural pentacyclic lupane-type triterpene exhibiting anticancer activity. Betulin derivatives bearing propynoyloxy and phosphate groups were prepared in an effort to improve the availability and efficacy of the drug. In this study, a comparative assessment of the in vitro anticancer activity of betulin and its four derivatives was carried out using two human breast cancer cell lines: SK-BR-3 and MCF-7. In both studied cell lines, 30-diethoxyphosphoryl-28-propynoylbetulin (compound 4) turned out to be the most powerful inhibitor of growth and inducer of cellular death. Detailed examination of that derivative pertained to the mechanisms underlying its anticancer action. Treatment with compound 4 decreased DNA synthesis and up-regulated p21WAF1/Cip1 mRNA and protein levels in both cell lines. On the other hand, that derivative caused a significant increase in cell death, as evidenced by increased lactate dehydrogenase (LDH) release and ethidium homodimer uptake. Shortly after the compound addition, an increased generation of reactive oxygen species and loss of mitochondrial membrane potential were detected. The activation of caspase-3 and fragmentation of genomic DNA suggested an apoptotic type of cell death. However, analysis of cellular morphology did not reveal any nuclear features typical of apoptosis. Despite necrosis-like morphology, dead cells exhibited activation of the cascade of caspases. These observations have led to the conclusion that compound 4 pushed cells to undergo a form of necrotic-like regulated cell demise

Anticancer Activity of the Acetylenic Derivative of Betulin Phosphate Involves Induction of Necrotic-Like Death in Breast Cancer Cells In Vitro

Betulin (BT) is a natural pentacyclic lupane-type triterpene exhibiting anticancer activity. Betulin derivatives bearing propynoyloxy and phosphate groups were prepared in an effort to improve the availability and efficacy of the drug. In this study, a comparative assessment of the in vitro anticancer activity of betulin and its four derivatives was carried out using two human breast cancer cell lines: SK-BR-3 and MCF-7. In both studied cell lines, 30-diethoxyphosphoryl-28-propynoylbetulin (compound 4) turned out to be the most powerful inhibitor of growth and inducer of cellular death. Detailed examination of that derivative pertained to the mechanisms underlying its anticancer action. Treatment with compound 4 decreased DNA synthesis and up-regulated p21WAF1/Cip1 mRNA and protein levels in both cell lines. On the other hand, that derivative caused a significant increase in cell death, as evidenced by increased lactate dehydrogenase (LDH) release and ethidium homodimer uptake. Shortly after the compound addition, an increased generation of reactive oxygen species and loss of mitochondrial membrane potential were detected. The activation of caspase-3 and fragmentation of genomic DNA suggested an apoptotic type of cell death. However, analysis of cellular morphology did not reveal any nuclear features typical of apoptosis. Despite necrosis-like morphology, dead cells exhibited activation of the cascade of caspases. These observations have led to the conclusion that compound 4 pushed cells to undergo a form of necrotic-like regulated cell demise