title: Molecular analysis of the apoptotic effects of BPA in acute myeloid leukemia cells.
abstract: BACKGROUND
  BPA (bisphenol A or 2,2-bis(4-hydroxy-phenol)propane) is present in the manufacture of polycarbonate plastic and epoxy resins, which can be used in impact-resistant safety equipment and baby bottles, as protective coatings inside metal food containers, and as composites and sealants in dentistry. Recently, attention has focused on the estrogen-like and carcinogenic adverse effects of BPA. Thus, it is necessary to investigate the cytotoxicity and apoptosis-inducing activity of this compound.
  
  
  METHODS
  Cell cycle, apoptosis and differentiation analyses; western blots.
  
  
  RESULTS
  BPA is able to induce cell cycle arrest and apoptosis in three different acute myeloid leukemias. Although some granulocytic differentiation concomitantly occurred in NB4 cells upon BPA treatment, the major action was the induction of apoptosis. BPA mediated apoptosis was caspase dependent and occurred by activation of extrinsic and intrinsic cell death pathways modulating both FAS and TRAIL and by inducing BAD phosphorylation in NB4 cells. Finally, also non genomic actions such as the early decrease of both ERK and AKT phosphorylation were induced by BPA thus indicating that a complex intersection of regulations occur for the apoptotic action of BPA.
  
  
  CONCLUSIONS
  BPA is able to induce apoptosis in leukemia cells via caspase activation and involvement of both intrinsic and extrinsic pathways of apoptosis.
authors.affiliation: Dipartimento di Patologia generale, Seconda Università di Napoli, Via L, De Crecchio 7, Napoli, Italy. paola.bontempo@unina2.it
authors.forename: Paola
authors.initials: P
authors.lastname: Bontempo
authors.forename: Luigi
authors.initials: L
authors.lastname: Mita
authors.forename: Antonella
authors.initials: A
authors.lastname: Doto
authors.forename: Marco
authors.initials: M
authors.lastname: Miceli
authors.forename: Angela
authors.initials: A
authors.lastname: Nebbioso
authors.forename: Ilaria
authors.initials: I
authors.lastname: Lepore
authors.forename: GianLuigi
authors.initials: G
authors.lastname: Franci
authors.forename: Roberta
authors.initials: R
authors.lastname: Menafra
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Carafa
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Conte
authors.forename: Floriana
authors.initials: F
authors.lastname: De Bellis
authors.forename: Fabio
authors.initials: F
authors.lastname: Manzo
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Cerbo
authors.forename: Rosaria
authors.initials: R
authors.lastname: Benedetti
authors.forename: Loredana
authors.initials: L
authors.lastname: D'Amato
authors.forename: Maria
authors.initials: M
authors.lastname: Marino
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bolli
authors.forename: Giovanna
authors.initials: G
authors.lastname: Del Pozzo
authors.forename: Nadia
authors.initials: N
authors.lastname: Diano
authors.forename: Marianna
authors.initials: M
authors.lastname: Portaccio
authors.forename: Gustavo D
authors.initials: GD
authors.lastname: Mita
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Vietri
authors.forename: Michele
authors.initials: M
authors.lastname: Cioffi
authors.forename: Ernesto
authors.initials: E
authors.lastname: Nola
authors.forename: Carmela
authors.initials: C
authors.lastname: Dell'aversana
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Sica
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Molinari
authors.forename: Lucia
authors.initials: L
authors.lastname: Altucci
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001559:Benzhydryl Compounds; D039521:CD11c Antigen / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010636:Phenols / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured; D051025:bcl-Associated Death Protein / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D039521:CD11c Antigen; D020169:Caspases; D048049:Extracellular Signal-Regulated MAP Kinases; D016166:Free Radical Scavengers; D010636:Phenols; D051057:Proto-Oncogene Proteins c-akt; D053221:TNF-Related Apoptosis-Inducing Ligand; D051025:bcl-Associated Death Protein; D019014:fas Receptor; C494819:BAD protein, human; C006780:bisphenol A; D000098826:Bisphenol A Compounds