title: Substituted diaryl diselenides: cytotoxic and apoptotic effect in human colon adenocarcinoma cells.
abstract: OBJECTIVE
  To investigate the effects and study the underlying cell death mechanisms of diaryl diselenides, including: diphenyl diselenide (C(6)H(5)Se)(2); 4-chlorodiphenyl diselenide (4-ClC(6)H(4)Se)(2); 3-(trifluoromethyl)-diphenyl diselenide (3-CF(3)C(6)H(4)Se)(2) and 4-methoxydiphenyl diselenide (4-MeOC(6)H(4)Se)(2), on the human colon adenocarcinoma cell line HT-29.
  
  
  METHODS
  The viability of HT-29 cells after exposure to the diaryl diselenides and its substituted structures was based on the MTT assay. To verify if cell death was mediated throughout apoptosis mechanisms, flow cytometry and real-time PCR (qPCR) analyses were conducted.
  
  
  RESULTS
  The MTT assay and flow cytometry analyses showed that (3-CF(3)C(6)H(4)Se)(2) and (4-MeOC(6)H(4)Se)(2) induced cytotoxicity through apoptosis mechanisms in HT-29 cells. qPCR revealed there was an up-regulation of pro-apoptotic (Bax, casapase-9, caspase-8, apoptosis-inducing factor (AIF) and Endonuclease G (EndoG)) and cell-cycle arrest genes (p53 and p21) and down-regulation of anti-apoptotic (Bcl-2 and survivin) and Myc genes.
  
  
  CONCLUSIONS
  These results demonstrate that (3-CF(3)C(6)H(4)Se)₂ and (4-MeOC(6)H(4)Se)(2) have the potential to induce apoptosis in HT-29 cells through the activation of caspase-dependent and independent pathways and through cell-cycle arrest.
authors.affiliation: Grupo de Oncologia Celular e Molecular, Programa de Pós-Graduação em Biotecnologia, Centro de Desenvolvimento Tecnológico/Biotecnologia, Universidade Federal de Pelotas, Capão do Leão, RS 96010-900, Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Nedel
authors.forename: Vinicius F
authors.initials: VF
authors.lastname: Campos
authors.forename: Diego
authors.initials: D
authors.lastname: Alves
authors.forename: Alan J A
authors.initials: AJ
authors.lastname: McBride
authors.forename: Odir A
authors.initials: OA
authors.lastname: Dellagostin
authors.forename: Tiago
authors.initials: T
authors.lastname: Collares
authors.forename: Lucielli
authors.initials: L
authors.lastname: Savegnago
authors.forename: Fabiana K
authors.initials: FK
authors.lastname: Seixas
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D016133:Polymerase Chain Reaction; D018036:Selenium Compounds / Q000737:chemistry / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018036:Selenium Compounds; D020169:Caspases