Comparative Analysis of the Cytotoxic Effect of a Complex of Selenium Nanoparticles Doped with Sorafenib, “Naked” Selenium Nanoparticles, and Sorafenib on Human Hepatocyte Carcinoma HepG2 Cells

Abstract

Despite the use of sorafenib as one of the most effective drugs for the treatment of liver cancer, its significant limitations remain—poor solubility, the need to use high doses with the ensuing complications on healthy tissues and organs, and the formation of cell resistance to the drug. At the same time, there is more and more convincing evidence of the anticancer effect of selenium-containing compounds and nanoparticles. The aim of this work was to develop a selenium–sorafenib nanocomplex and study the molecular mechanisms of its anticancer effect on human hepatocyte carcinoma cells, where nanoselenium is not only a sorafenib transporter, but also an active compound. We have created a selenium–sorafenib nanocomplex based on selenium nanoparticles with size 100 nm. Using vitality tests, fluorescence microscopy, and PCR analysis, it was possible to show that selenium nanoparticles, both by themselves and doped with sorafenib, have a pronounced pro-apoptotic effect on HepG2 cells with an efficiency many times greater than that of sorafenib (So). “Naked” selenium nanoparticles (SeNPs) and the selenium–sorafenib nanocomplex (SeSo), already after 24 h of exposure, lead to the induction of the early stages of apoptosis with the transition to the later stages with an increase in the incubation time up to 48 h. At the same time, sorafenib, at the studied concentrations, began to exert a proapoptotic effect only after 48 h. Under the action of SeNPs and SeSo, both classical pathways of apoptosis induction and ER-stress-dependent pathways involving Ca2+ ions are activated. Thus, sorafenib did not cause the generation of Ca2+ signals by HepG2 cells, while SeNPs and SeSo led to the activation of the Ca2+ signaling system of cells. At the same time, the selenium–sorafenib nanocomplex turned out to be more effective in activating the Ca2+ signaling system of cells, inducing apoptosis and ER stress by an average of 20–25% compared to “naked” selenium nanoparticles. Our data on the mechanisms of action and the created nanocomplex are promising as a platform for the creation of highly selective and effective drugs with targeted delivery to tumors.

Molecular Mechanisms of the Cytotoxic Effect of Recombinant Selenoprotein SELENOM on Human Glioblastoma Cells

“…It is known that selenium and selenium-containing organic and inorganic compounds have a cytotoxic effect on various cancer cells [ 21 , 22 , 23 , 24 , 25 , 26 ]. Relatively recently, a similar cytotoxic effect of selenium nanoparticles was demonstrated [ 18 , 27 , 28 , 29 , 30 , 31 , 32 ]. However, selenium-containing proteins still play an important role, as this trace element is part of the active catalytic centers in the form of the amino acid selenocysteine.…”

Selenium Nanoparticles Based on Morinda officinalis Polysaccharides: Characterization, Anti-Cancer Activities, and Immune-Enhancing Activities Evaluation In Vitro

“…Previous studies have shown that different methods can induce apoptosis in HepG2 cells. It has been reported that selenium–sorafenib complexes can effectively activate the Ca 2+ signaling system and cause endoplasmic reticulum stress [ 40 ], while glucan-selenium nanoparticles (Glucan-SeNPs) can activate Caspase-3 and Caspase-9 [ 41 ]. This experiment provides a basis for exploring the specific mechanism of apoptosis in the future.…”

Novel Therapeutic Potentials of Taxifolin for Obesity-Induced Hepatic Steatosis, Fibrogenesis, and Tumorigenesis

“…Given that the NASH pathogenesis is heterogenous and diverse in humans, these pleiotropic effects of Taxifolin may be advantageous for clinical practice. In this respect, recent studies developed a novel nanocomplex of selenium with sorafenib [ 42 ] or Taxifolin [ 43 ], which exhibits more beneficial effects than those of single molecules in vitro in terms of anticancer or neuroprotective effects. Accordingly, the use of the nanocomplex would be a valuable therapeutic option for NASH.…”