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Selenite-Induced Toxicity in Cancer Cells Is Mediated by Metabolic Generation of Endogenous Selenium Nanoparticles
Bao, P; Chen, Z; Tai, RZ; Shen, HM; Martin, FL; Zhu, YG
2015
Source PublicationJOURNAL OF PROTEOME RESEARCH
Volume14Issue:2Pages:1127—1136
Subtype期刊文献
AbstractSelenite has been a touted cancer chemopreventative agent but generates conflicting outcomes. Multiple mechanisms of selenite cytotoxicity in cancer cells are thought to be induced by metabolites of selenite. We observed that intracellular metabolism of selenite generates endogenous selenium nanoparticles (SeNPs) in cancer cells. Critical proteins that bind with high affinity to elemental selenium during SeNPs self-assembly were identified through proteomics analysis; these include glycolytic enzymes, insoluble tubulin, and heat shock proteins 90 (HSP90). Sequestration of glycolytic enzymes by SeNPs dramatically inhibits ATP generation, which leads to functional and structural disruption of mitochondria. Transcriptome sequencing showed tremendous down-regulation of mitochondrial respiratory NADH dehydrogenase (complex I), cytochrome c oxidase (complex IV), and ATP synthase (complex V) in response to glycolysis-dependent mitochondrial dysfunction. Sequestration of insoluble tubulin led to microtubule depolymerization, altering microtubule dynamics. HSP90 sequestration led to degradation of its downstream effectors via autophagy, ultimately resulting in a cell-signaling switch to apoptosis. Additionally, the surface effects of SeNPs generated oxidative stress, thus contributing to selenite cytotoxicity. Herein, we reveal that the multiple mechanisms of selenite-induced cytotoxicity are caused by endogenous protein-assisted self-assembly of SeNPs and suggest that endogenous SeNPs could potentially be the primary cause of selenite-induced cytotoxicity.
KeywordSodium-selenite Mitochondrial Damage Oxidative Stress Hepg2 Cells Apoptosis Cytotoxicity Thioredoxin Attenuation Glycolysis Expression
Indexed BySCI
Language英语
Document Type期刊论文
Identifierhttp://ir.sinap.ac.cn/handle/331007/24560
Collection中科院上海应用物理研究所2011-2020年
Recommended Citation
GB/T 7714
Bao, P,Chen, Z,Tai, RZ,et al. Selenite-Induced Toxicity in Cancer Cells Is Mediated by Metabolic Generation of Endogenous Selenium Nanoparticles[J]. JOURNAL OF PROTEOME RESEARCH,2015,14(2):1127—1136.
APA Bao, P,Chen, Z,Tai, RZ,Shen, HM,Martin, FL,&Zhu, YG.(2015).Selenite-Induced Toxicity in Cancer Cells Is Mediated by Metabolic Generation of Endogenous Selenium Nanoparticles.JOURNAL OF PROTEOME RESEARCH,14(2),1127—1136.
MLA Bao, P,et al."Selenite-Induced Toxicity in Cancer Cells Is Mediated by Metabolic Generation of Endogenous Selenium Nanoparticles".JOURNAL OF PROTEOME RESEARCH 14.2(2015):1127—1136.
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