title: Selenoglycoproteins attenuate adhesion of tumor cells to the brain microvascular endothelium via a process involving NF-κB activation.
abstract: Selenium-containing compounds and selenized yeast have anticancer properties. In order to address possible mechanisms involved in these effects, selenoglycoproteins (SGPs) were extracted from selenium-enriched yeast at pH 4.0 and 6.5 (the fractions are called SGP40 and SGP65, respectively), followed by evaluation of their impact on the interactions of lung and breast tumor cells with human brain microvascular endothelial cells (HBMECs). Extracted SGPs, especially SGP40, significantly inhibited adhesion of tumor cells to HBMECs and their transendothelial migration. Because the active components of SGPs are unknown, small selenium-containing compounds [leucyl-valyl-selenomethionyl-arginine (LVSe-MR) and methylselenoadenosine (M-Se-A)], which are normally present in selenized yeast, were introduced as additional treatment groups. Treatment of HBMECs with SGP40, LVSe-MR and M-Se-A induced changes in gene signatures, which suggested a central involvement of nuclear factor (NF)-κB-dependent pathway. These observations were confirmed in the subsequent analysis of NF-κB DNA binding activity, quantitative measurements of the expression of selected genes and proteins, and tumor cell adhesion assay with a specific NF-κB inhibitor as the additional treatment factor. These findings indicate that specific organic selenium-containing compounds have the ability to inhibit tumor cell adhesion to brain endothelial cells via down-regulation of NF-κB. SGPs appear to be more effective than small selenium-containing compounds, suggesting the role of not only selenium but also the glycoprotein component in the observed protective impact.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Jagoda K
authors.initials: JK
authors.lastname: Wrobel
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Jeong June
authors.initials: JJ
authors.lastname: Choi
authors.affiliation: Nutrigenomics Research Center, Alltech, Nicholasville, KY 40356, USA.
authors.forename: Rijin
authors.initials: R
authors.lastname: Xiao
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Sung Yong
authors.initials: SY
authors.lastname: Eum
authors.affiliation: Nutrigenomics Research Center, Alltech, Nicholasville, KY 40356, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kwiatkowski
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Gretchen
authors.initials: G
authors.lastname: Wolff
authors.affiliation: Nutrigenomics Research Center, Alltech, Nicholasville, KY 40356, USA.
authors.forename: Leya
authors.initials: L
authors.lastname: Spangler
authors.affiliation: Nutrigenomics Research Center, Alltech, Nicholasville, KY 40356, USA.
authors.forename: Ronan F
authors.initials: RF
authors.lastname: Power
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Jerzy Kukuczka Academy of Physical Education, Katowice 40-065, Poland. Electronic address: mtoborek@med.miami.edu.
authors.forename: Michal
authors.initials: M
authors.lastname: Toborek
mesh_terms: D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D001921:Brain / Q000098:blood supply / Q000166:cytology / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006023:Glycoproteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D055806:Microvessels / Q000166:cytology / Q000187:drug effects; D016328:NF-kappa B / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D016566:Organoselenium Compounds / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology*; D012643:Selenium / Q000378:metabolism; D012645:Selenomethionine / Q000031:analogs & derivatives / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D051140:Selenoproteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology*; D057705:Transendothelial and Transepithelial Migration / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D006023:Glycoproteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D016566:Organoselenium Compounds; D029701:Saccharomyces cerevisiae Proteins; D051140:Selenoproteins; D012645:Selenomethionine; D012643:Selenium
keywords: Adhesion; Brain; NF-κB; Selenium; Transendothelial migration; Tumor cell motility