title: 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.
authors.affiliation: Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China. pbao@iue.ac.cn and Ningbo Urban Environment Observation and Research Station, Chinese Academy of Sciences, Ningbo 315800, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Bao
authors.affiliation: State Key Lab of Urban and Regional Ecology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, P. R. China.
authors.forename: Song-Can
authors.initials: SC
authors.lastname: Chen
authors.affiliation: State Key Lab of Urban and Regional Ecology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, P. R. China.
authors.forename: Ke-Qing
authors.initials: KQ
authors.lastname: Xiao
mesh_terms: D017306:Annexin A2 / Q000378:metabolism; D001692:Biological Transport; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D020887:Selenious Acid / Q000494:pharmacology*; D012643:Selenium / Q000737:chemistry
chemical_list: C472822:ANXA2 protein, human; D017306:Annexin A2; D011451:Prostaglandin-Endoperoxide Synthases; D020887:Selenious Acid; D012643:Selenium