Ca2+-Dependent Effects of the Selenium-Sorafenib Nanocomplex on Glioblastoma Cells and Astrocytes of the Cerebral Cortex: Anticancer Agent and Cytoprotector

Abstract

Despite the fact that sorafenib is recommended for the treatment of oncological diseases of the liver, kidneys, and thyroid gland, and recently it has been used for combination therapy of brain cancer of various genesis, there are still significant problems for its widespread and effective use. Among these problems, the presence of the blood–brain barrier of the brain and the need to use high doses of sorafenib, the existence of mechanisms for the redistribution of sorafenib and its release in the brain tissue, as well as the high resistance of gliomas and glioblastomas to therapy should be considered the main ones. Therefore, there is a need to create new methods for delivering sorafenib to brain tumors, enhancing the therapeutic potential of sorafenib and reducing the cytotoxic effects of active compounds on the healthy environment of tumors, and ideally, increasing the survival of healthy cells during therapy. Using vitality tests, fluorescence microscopy, and molecular biology methods, we showed that the selenium-sorafenib (SeSo) nanocomplex, at relatively low concentrations, is able to bypass the mechanisms of glioblastoma cell chemoresistance and to induce apoptosis through Ca2+-dependent induction of endoplasmic reticulum stress, changes in the expression of selenoproteins and selenium-containing proteins, as well as key kinases-regulators of oncogenicity and cell death. Selenium nanoparticles (SeNPs) also have a high anticancer efficacy in glioblastomas, but are less selective, since SeSo in cortical astrocytes causes a more pronounced activation of the cytoprotective pathways.

Current Trends on the Involvement of Zinc, Copper, and Selenium in the Process of Hepatocarcinogenesis

“…For example, SeNPs initiated the chemosensitivity of fluorouracil nanoparticles in the breast and colon cancer cell lines [ 152 ]. Another study documented that the Se–sorafenib nanocomplex could bypass the chemoresistance in glioblastoma cells [ 153 ]. It is of particular interest that this Se–sorafenib nanocomplex induced the apoptosis of cancer cells via Ca 2+ -dependent endoplasmic reticulum stress.…”

Selenium Nanoparticles in Protecting the Brain from Stroke: Possible Signaling and Metabolic Mechanisms

“…On the other hand, as indicated above, nanoselenium affects the expression of ER-resident selenoproteins involved in the regulation of intracellular Ca 2+ ion concentration. It was found that the incubation of cortical astrocytes with SeNPs for 24 h leads to the depletion of the Ca 2+ pool of the ER, and this depletion of the Ca 2+ pool is correlated with the activation of proteins responsible for the activation of adaptive ER stress [ 172 ]. However, these mechanisms require detailed study.…”

A Review of the Antibacterial, Fungicidal and Antiviral Properties of Selenium Nanoparticles

“…Hyaluronic acid (A549 cells), ATP (depletion of mitochondrial membrane potential and oxidative stress) and other agents were also described [69,70]. The addition of anticancer agents (sorafenib) to SeNPs significantly increases the activity of others against aggressive cancer lines (increased calcium entry, ER stress and apoptosis of HepG2, gliablastoma A-172) [49,71,72]. Oridoni/SeNP composites have anticancer activity and reduce the viability of RAW264.7, KYSE-150 and EC970 cancer cells by ~50% [73].…”