title: Loss of Selenium-Binding Protein 1 Decreases Sensitivity to Clastogens and Intracellular Selenium Content in HeLa Cells.
abstract: Selenium-binding protein 1 (SBP1) is not a selenoprotein but structurally binds selenium. Loss of SBP1 during carcinogenesis usually predicts poor prognosis. Because genome instability is a hallmark of cancer, we hypothesize that SBP1 sequesters cellular selenium and sensitizes cancer cells to DNA-damaging agents. To test this hypothesis, we knocked down SBP1 expression in HeLa cervical cancer cells by employing a short hairpin RNA (shRNA) approach. Reduced sensitivity to hydrogen peroxide, paraquat and camptothecin, reactive oxygen species content, and intracellular retention of selenium after selenomethionine treatment were observed in SBP1 shRNA HeLa cells. Results from Western analyses showed that treatment of HeLa cells with selenomethionine resulted in increased SBP1 protein expression in a dose-dependent manner. Knockdown of SBP1 rendered HeLa cells increased expression of glutathione peroxidase-1 but not glutathione peroxidase-4 protein levels and accelerated migration from a wound. Altogether, SBP1 retains supplemental selenium and sensitizes HeLa cancer cells to clastogens, suggesting a new cancer treatment strategy by sequestering selenium through SBP1.
authors.affiliation: Department of Food Quality and Safety, College of Food Science and Engineering, Jilin University, Changchun, Jilin Province, 130062, China.|Department of Nutrition and Food Science, University of Maryland, College Park, Maryland 20742, United States of America.
authors.forename: Changhui
authors.initials: C
authors.lastname: Zhao
authors.affiliation: United States Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, North Dakota 58202, United States of America.
authors.forename: Huawei
authors.initials: H
authors.lastname: Zeng
authors.affiliation: Department of Nutrition and Food Science, University of Maryland, College Park, Maryland 20742, United States of America.
authors.forename: Ryan T Y
authors.initials: RT
authors.lastname: Wu
authors.affiliation: Department of Food Science, Nutrition & Health Promotion, Mississippi State University, Mississippi State, Mississippi 39762, United States of America.
authors.forename: Wen-Hsing
authors.initials: WH
authors.lastname: Cheng
mesh_terms: D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D004249:DNA Damage; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects* / Q000378:metabolism*; D009153:Mutagens / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D012643:Selenium / Q000378:metabolism*; D051137:Selenium-Binding Proteins / Q000172:deficiency* / Q000235:genetics*; D012645:Selenomethionine / Q000494:pharmacology
chemical_list: D009153:Mutagens; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C495175:SELENBP1 protein, human; D051137:Selenium-Binding Proteins; D012645:Selenomethionine; D012643:Selenium