title: PVM/MA-shelled selol nanocapsules promote cell cycle arrest in A549 lung adenocarcinoma cells.
abstract: BACKGROUND
  Selol is an oily mixture of selenitetriacylglycerides that was obtained as a semi-synthetic compound containing selenite. Selol is effective against cancerous cells and less toxic to normal cells compared with inorganic forms of selenite. However, Selol's hydrophobicity hinders its administration in vivo. Therefore, the present study aimed to produce a formulation of Selol nanocapsules (SPN) and to test its effectiveness against pulmonary adenocarcinoma cells (A549).
  
  
  RESULTS
  Nanocapsules were produced through an interfacial nanoprecipitation method. The polymer shell was composed of poly(methyl vinyl ether-co-maleic anhydride) (PVM/MA) copolymer. The obtained nanocapsules were monodisperse and stable. Both free Selol (S) and SPN reduced the viability of A549 cells, whereas S induced a greater reduction in non-tumor cell viability than SPN. The suppressor effect of SPN was primarily associated to the G2/M arrest of the cell cycle, as was corroborated by the down-regulations of the CCNB1 and CDC25C genes. Apoptosis and necrosis were induced by Selol in a discrete percentage of A549 cells. SPN also increased the production of reactive oxygen species, leading to oxidative cellular damage and to the overexpression of the GPX1, CYP1A1, BAX and BCL2 genes.
  
  
  CONCLUSIONS
  This study presents a stable formulation of PVM/MA-shelled Selol nanocapsules and provides the first demonstration that Selol promotes G2/M arrest in cancerous cells.
authors.affiliation: Institute of Biological Sciences, Molecular Biology Programme, University of Brasília, Brasília, DF, 70910-900, Brazil. ludmillarsouza@gmail.com.
authors.forename: Ludmilla Regina
authors.initials: LR
authors.lastname: de Souza
authors.affiliation: Institute of Biological Sciences, University of Brasília, Brasília, DF, 70910-900, Brazil. luismuehlmann@yahoo.de.
authors.forename: Luis Alexandre
authors.initials: LA
authors.lastname: Muehlmann
authors.affiliation: Institute of Biological Sciences, Molecular Biology Programme, University of Brasília, Brasília, DF, 70910-900, Brazil. mayara.simonelly@gmail.com.
authors.forename: Mayara Simonelly Costa
authors.initials: MS
authors.lastname: Dos Santos
authors.affiliation: Institute of Biological Sciences, University of Brasília, Brasília, DF, 70910-900, Brazil. rayaneganassin@hotmail.com.
authors.forename: Rayane
authors.initials: R
authors.lastname: Ganassin
authors.affiliation: Biomedical Research Center (CINBIO), Institute of Biomedical Research of Vigo, University of Vigo, Vigo, Pontevedra, 36310, Spain. rosana.simon@uvigo.es.
authors.forename: Rosana
authors.initials: R
authors.lastname: Simón-Vázquez
authors.affiliation: Institute of Biological Sciences, University of Brasília, Brasília, DF, 70910-900, Brazil. bygra1@gmail.com.
authors.forename: Graziella Anselmo
authors.initials: GA
authors.lastname: Joanitti
authors.affiliation: Institute of Physics, Polish Academy of Sciences, Warsaw, 02-668, Poland. mosin@ifpan.edu.pl.
authors.forename: Ewa
authors.initials: E
authors.lastname: Mosiniewicz-Szablewska
authors.affiliation: Department of Bioanalysis and Drugs Analysis, Warsaw Medical University, Warsaw, 02-097, Poland. piotr.suchocki@wum.edu.pl.|Department of Pharmaceutical Chemistry, National Medicines Institute, Warsaw, 00-725, Poland. piotr.suchocki@wum.edu.pl.
authors.forename: Piotr
authors.initials: P
authors.lastname: Suchocki
authors.affiliation: Institute of Physics, University of Brasília, Brasília, DF, 70910-900, Brazil. pcmor@unb.br.|School of Automation, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China. pcmor@unb.br.
authors.forename: Paulo César
authors.initials: PC
authors.lastname: Morais
authors.affiliation: Biomedical Research Center (CINBIO), Institute of Biomedical Research of Vigo, University of Vigo, Vigo, Pontevedra, 36310, Spain. africa@uvigo.es.
authors.forename: África
authors.initials: Á
authors.lastname: González-Fernández
authors.affiliation: Institute of Biological Sciences, University of Brasília, Brasília, DF, 70910-900, Brazil. razevedo@unb.br.
authors.forename: Ricardo Bentes
authors.initials: RB
authors.lastname: Azevedo
authors.affiliation: Institute of Biological Sciences, University of Brasília, Brasília, DF, 70910-900, Brazil. snbao@unb.br.
authors.forename: Sônia Nair
authors.initials: SN
authors.lastname: Báo
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000648:ultrastructure; D000077192:Adenocarcinoma of Lung; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor / Q000187:drug effects / Q000648:ultrastructure; D056744:Cyclin B1 / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005979:Glutathione Peroxidase / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000648:ultrastructure; D008298:Maleates / Q000737:chemistry*; D053769:Nanocapsules / Q000737:chemistry*; D057145:Nanoshells / Q000737:chemistry; D011095:Polyethylenes / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism; D018036:Selenium Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D013816:Thermodynamics; D020687:cdc25 Phosphatases / Q000235:genetics; D000094765:Glutathione Peroxidase GPX1
chemical_list: D000970:Antineoplastic Agents; C534699:CCNB1 protein, human; D056744:Cyclin B1; D008298:Maleates; D053769:Nanocapsules; D011095:Polyethylenes; D017382:Reactive Oxygen Species; D018036:Selenium Compounds; C105370:selol; C043105:poly(methyl vinyl ether-co-maleic anhydride); D005979:Glutathione Peroxidase; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human