Dynamic equilibrium of endogenous selenium nanoparticles in selenite-exposed cancer cells: a deep insight into the interaction between endogenous SeNPs and proteins

Abstract

Elemental selenium (Se) was recently found to exist as endogenous nanoparticles (i.e., SeNPs) in selenite-exposed cancer cells. By sequestrating critical intracellular proteins, SeNPs appear capable of giving rise to multiple cytotoxicity mechanisms including inhibition of glycolysis, glycolysis-dependent mitochondrial dysfunction, microtubule depolymerization and inhibition of autophagy. In this work, we reveal a dynamic equilibrium of endogenous SeNP assembly and disassembly in selenite-exposed H157 cells. Endogenous SeNPs are observed both in the cytoplasm and in organelles. There is an increase in endogenous SeNPs between 24 h and 36 h, and a decrease between 36 h and 72 h according to transmission electron microscopy results and UV-Vis measurements. These observations imply that elemental Se in SeNPs could be oxidized back into selenite by scavenging superoxide radicals and ultimately re-reduced into selenide; then the assembly and disassembly of SeNPs proceed simultaneously with the sequestration and release of SeNP high-affinity proteins. There is also a possibility that the reduction of elemental Se to selenide pathway may lie in selenite-exposed cancer cells, which results in the assembly and disassembly of endogenous SeNPs. Genome-wide expression analysis results show that endogenous SeNPs significantly altered the expression of 504 genes, compared to the control. The endogenous SeNPs induced mitochondrial impairment and decreasing of the annexin A2 level can lead to inhibition of cancer cell invasion and migration. This dynamic flux of endogenous SeNPs amplifies their cytotoxic potential in cancer cells, thus provide a starting point to design more efficient intracellular self-assembling systems for overcoming multidrug resistance.

Green synthesis of selenium nanoparticles using<em> Acinetobacter</em> sp. SW30: optimization, characterization and its anticancer activity in breast cancer cells

“…49 It has been reported that elemental selenium exists as endogenous SeNPs in H157 cell line and induces cytotoxicity by many mechanisms such as inhibition of glycolysis, glycolysis-dependent mitochondrial dysfunction, and so on. 50 Microscopic observation of 4T1 cells treated with SeNPs showed a dose-dependent reduction in cell number, loss of cell-to-cell contact and cell shrinkage ( Figure 10A-D). The same cellular morphologic changes were observed when MCF-7 cells were treated with selenium nanorods synthesized by S. bikiniensis strain Ess_amA-1.…”

“…38 BSeNPs are also reported to exhibit significant anticancer activity against H157 lung cancer cell line, fibrosarcoma cell line and A375 human melanoma. 5,48,50,51 Oral administration of SeNPs can enhance immune response in mice bearing 4T1 breast cancer tumor. 52 …”

Nano-Se Assimilation and Action in Poultry and Other Monogastric Animals: Is Gut Microbiota an Answer?

“…There are very attractive suggestions that gut microbiota can oxidize nano-Se into selenite/selenate or reduce it into H 2 Se with the following synthesis of selenoproteins [ 6 , 7 ]. Recently, some experimental evidence have been provided to prove that nano-Se particles can be dissolved and oxidized to inorganic oxoanions of Se in the gut in the presence of microbiota before their absorption [ 6 ].…”

“…Recently, some experimental evidence have been provided to prove that nano-Se particles can be dissolved and oxidized to inorganic oxoanions of Se in the gut in the presence of microbiota before their absorption [ 6 ]. Furthermore, a hypothetical schematic diagram showing an intracellular dynamic cycle of endogenous selenium nanoparticles (SeNPs) was proposed [ 7 ]. In fact, it was suggested that elemental selenium could be re-oxidized by superoxide radicals into selenite.…”

“…Alternatively, elemental selenium can be reduced/converted into selenide by a selenite-respiring bacterium (for example, Bacillus selenitireducens ). The aforementioned reaction conducted by the bacteria with the incomplete oxidation of the electron donor lactate to acetate as follows was presented as follows [ 7 ]: …”