title: A new erythrocyte-based biochemical approach to predict the antiproliferative effects of heterocyclic scaffolds: The case of indolone.
abstract: BACKGROUND
  The indole core is a key structural feature of many natural products and biomolecules with broad spectrum chemotherapeutic properties. Some of us have recently synthesized a library of biologically promising indolone-based compounds. The present study focuses on the effects of one of them, namely DPIT, on human erythrocytes.
  
  
  METHODS
  We have examined the influence of DPIT on band 3 protein, intracellular ATP concentration and transport, caspase 3 activation, metabolic adaptation and membrane stability.
  
  
  RESULTS
  Our study elucidates that DPIT, intercalated into the phospholipid bilayer, decreases the anion transport, the intracellular ATP concentration and the cytosolic pH, inducing a direct activation of caspase 3.
  
  
  CONCLUSIONS
  Starting from the metabolic similarity between erythrocytes and cancer cells, we investigate how the metabolic derangements and membrane alterations induced by selected heterocycles could be related to the antiproliferative effects.
  
  
  CONCLUSIONS
  Our work aims to propose a new model of study to predict the antiproliferative effects of heterocyclic scaffolds, pointing out that only one of the listed conditions would be unfavorable to the life cycle of neoplastic cells.
authors.affiliation: Department of Chemical Sciences, University of Messina, V.le F. Stagno d'Alcontres 31, 98166 Messina, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Scala
authors.affiliation: Department of Chemical Sciences, University of Messina, V.le F. Stagno d'Alcontres 31, 98166 Messina, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Ficarra
authors.affiliation: Department of Chemical Sciences, University of Messina, V.le F. Stagno d'Alcontres 31, 98166 Messina, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Russo
authors.affiliation: Department of Chemical Sciences, University of Messina, V.le F. Stagno d'Alcontres 31, 98166 Messina, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Barreca
authors.affiliation: Virology and Microbiology AOOR Papardo-Piemonte, V.le F. Stagno d'Alcontres, 98166 Messina, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Giunta
authors.affiliation: Department of Chemical Sciences, University of Messina, V.le F. Stagno d'Alcontres 31, 98166 Messina, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Galtieri
authors.affiliation: Department of Chemical Sciences, University of Messina, V.le F. Stagno d'Alcontres 31, 98166 Messina, Italy. Electronic address: ggrassi@unime.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Grassi
authors.affiliation: Department of Chemical Sciences, University of Messina, V.le F. Stagno d'Alcontres 31, 98166 Messina, Italy.
authors.forename: Ester
authors.initials: E
authors.lastname: Tellone
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects*; D005434:Flow Cytometry; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008954:Models, Biological; D015394:Molecular Structure; D018384:Oxidative Stress / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism
chemical_list: C000595203:2,2'-dimethyl-6,6'-diphenyl-6,6',7,7'-tetrahydro-1H,1'H-2,3'-biindole-3,4,4'(2H,5H,5'H)-trione; D006571:Heterocyclic Compounds; D007211:Indoles; D013481:Superoxides; D000255:Adenosine Triphosphate; D053148:Caspase 3
keywords: ATP transport; Anion transport; Antiproliferation; Caspase 3; Heterocycle; Red blood cell