Molecular analysis of the apoptotic effects of BPA in acute myeloid leukemia cells.
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.
Bontempo
Paola
P
Dipartimento di Patologia generale, Seconda Università di Napoli, Via L, De Crecchio 7, Napoli, Italy. paola.bontempo@unina2.it
Mita
Luigi
L
Doto
Antonella
A
Miceli
Marco
M
Nebbioso
Angela
A
Lepore
Ilaria
I
Franci
GianLuigi
G
Menafra
Roberta
R
Carafa
Vincenzo
V
Conte
Mariarosaria
M
De Bellis
Floriana
F
Manzo
Fabio
F
Di Cerbo
Vincenzo
V
Benedetti
Rosaria
R
D'Amato
Loredana
L
Marino
Maria
M
Bolli
Alessandro
A
Del Pozzo
Giovanna
G
Diano
Nadia
N
Portaccio
Marianna
M
Mita
Gustavo D
GD
Vietri
Maria Teresa
MT
Cioffi
Michele
M
Nola
Ernesto
E
Dell'aversana
Carmela
C
Sica
Vincenzo
V
Molinari
Anna Maria
AM
Altucci
Lucia
L
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
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