Silica nanoparticles (SiNPs) are one of the most commonly used nanomaterials in various medical applications. However, possible mechanisms of the toxicity caused by SiNPs remain unclear. The study presented here provides novel information on molecular and cellular effects of SiNPs in glioblastoma LBC3 and LN-18 cells. It has been demonstrated that SiNPs of 7 nm, 5–15 nm and 10–20 nm induce time- and dose-dependent cytotoxicity in LBC3 and LN-18 cell lines. In contrast to glioblastoma cells, we observed only weak reduction in viability of normal skin fibroblasts treated with SiNPs. Furthermore, in LBC3 cells treated with 5–15 nm SiNPs we noticed induction of apoptosis and necrosis, while in LN-18 cells only necrosis. The 5–15 nm SiNPs were also found to cause oxidative stress, a loss in mitochondrial membrane potential, and changes in the ultrastructure of the mitochondria in LBC3 cells. Quantitative real-time PCR results showed that in LBC3 cells the mRNA levels of pro-apoptotic genes Bim, Bax, Puma, and Noxa were significantly upregulated. An increase in activity of caspase-9 in these cells was also observed. Moreover, the activation of SiNP-induced autophagy was demonstrated in LBC3 cells as shown by an increase in LC3-II/LC3-I ratio, the upregulation of Atg5 gene and an increase in AVOs-positive cells. In conclusion, this research provides novel information concerning molecular mechanisms of apoptosis and autophagy in LBC3 cells.
1 December 2005 in Biochimica et Biophysica Acta (BBA) - Biomembranes
Caffeic acid (CA) is a phenolic compound synthesized by all plant species. It constitutes the main hydroxycinnamic acid found in human diet and presents a variety of beneficial effects including anticancer activity. Current data suggests essential role of the interplay between anticancer drugs and the cell membrane. Given this, biophysical interactions between CA and cancer cells or biomimetic membranes were investigated. Glioblastoma cell line U118MG and colorectal adenocarcinoma cell line DLD-1, as well as lipid bilayers and liposomes, were used as in vitro models. Electrophoretic light scattering was used to assess the effect of CA on the surface charge of cancer cells and liposomal membranes. Electrochemical impedance spectroscopy was chosen to evaluate CA-dependent modulatory effect on the electrical capacitance and electrical resistance of the bilayers. Our results suggest that CA fulfills physicochemical criteria determining drug-like properties of chemical compounds, and may serve as a potential cytostatic agent in cancer treatment.
In recent years, many scientists have studied the effects of polymer micro- and nanostructures on living organisms. As it turns out, plastic can be a component of the blood of livestock, eaten by humans around the globe. Thus, it seems important to investigate possible changes in the physicochemical parameters and morphology of the cell membranes of blood morphotic elements (red blood cells and platelets) under the influence of polymer particles. The article presents research in which cell membranes were exposed to plain polystyrene (PS) and amino-functionalized polystyrene (PS-NH2) of two different sizes. The polymers were characterized by infrared spectroscopy and dynamic light-scattering methods. To analyze possible changes caused by polymer exposure in the structure of the membranes, their zeta potentials were measured using the electrophoretic light-scattering technique. The concentration of the polymers, as well as the exposure time, were also taken into the consideration during the research. Based on the obtained results, we concluded that 100 and 200 nm PS, as well as 100 nm PS-NH2, internalize into the cells. On the contrary, 200 nm PS-NH2 particles attach to cell membranes. Our study clearly shows that particle size and surface chemistry determine the interaction with biological membranes.