Selenite-Induced Toxicity in Cancer Cells Is Mediated by Metabolic Generation of Endogenous Selenium Nanoparticles

CORC > 上海应用物理研究所 > 中国科学院上海应用物理研究所 > 中科院上海应用物理研究所2011-2017年

	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
刊名	JOURNAL OF PROTEOME RESEARCH
	2015
卷号	14 期号:2 页码:1127—1136
关键词	SODIUM-SELENITE MITOCHONDRIAL DAMAGE OXIDATIVE STRESS HEPG2 CELLS APOPTOSIS CYTOTOXICITY THIOREDOXIN ATTENUATION GLYCOLYSIS EXPRESSION
英文摘要	Selenite 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.
收录类别	SCI
语种	英语
公开日期	2015-12-24
内容类型	期刊论文
源URL	[http://ir.sinap.ac.cn/handle/331007/24560]
专题	上海应用物理研究所_中科院上海应用物理研究所2011-2017年
推荐引用方式 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.