Comparative Study of the Anticancer Effects of Selenium Nanoparticles and Selenium Nanorods: Regulation of Ca2+ Signaling, ER Stress and Apoptosis

Abstract

The anti-cancer effects of selenium sources are well known. Among other things, selenium has been shown to have a pleiotropic effect, causing cancer cell death without affecting the healthy cell’s viability, or, in the case of brain cells, has a cytoprotective effect. This feature of selenium determined its use in medicine and its use as part of dietary supplements. In recent years, selenium in the form of nanoparticles has received increased attention. Selenium nanoparticles also have anti-cancer effects, and their use appears to be more effective at significantly lower doses compared to other sources of selenium. The shape and size of nanoparticles largely affect the efficiency of nanoselenium application. We obtained two different types of selenium nanoparticles via the laser ablation technique—spherical selenium nanoparticles (SeNPs) about 100 nm in diameter and grown selenium nanorods (SeNrs) about 1 μm long and about 100 nm thick. We compared the anti-cancer efficacy of these two types of selenium nanoparticles using inhibitory analysis, PCR analysis and fluorescence microscopy. It turned out that both types of nanoparticles with high efficiency dose-dependently activate apoptosis in the human glioblastoma cell line A-172, as the most aggressive type of brain tumor. Apoptosis induction was determined not only by the concentration of nanoparticles, but also by the time. It was shown that SeNrs induce the process of apoptosis in glioblastoma cells more efficiently during 24 h of exposure and their effect is enhanced after 48 h without activation of necrosis, whereas the use of spherical SeNPs after 48 h of exposure can cause necrosis in some glioblastoma cells. It has been shown that Ca2+ signals of glioblastoma cells are significantly different for SeNPs and SeNrs. SeNPs cause a dose-dependent transient increase in the number of Ca2+ ions in the cell cytosol ([Ca2+]i), while SeNrs cause a slow rise in [Ca2+]i reaching a new stationary level, which may determine the cytotoxic effects of nanoparticles. It turned out that SeNPs and SeNrs cause depletion of the Ca2+ depot of the endoplasmic reticulum and ER-stress, which correlates with increased expression of genes encoding proapoptotic proteins. In our study, it was found that SeNPs do not activate the Ca2+ signaling system of healthy L-929 mouse fibroblast cells, while SeNrs activate a moderate slow growth in [Ca2+]i. That fact could indicate a lower selectivity of the SeNrs action.