Open Access Research

Molecular analysis of the apoptotic effects of BPA in acute myeloid leukemia cells

Paola Bontempo12, Luigi Mita123, Antonella Doto1, Marco Miceli1, Angela Nebbioso1, Ilaria Lepore1, GianLuigi Franci1, Roberta Menafra1, Vincenzo Carafa1, Mariarosaria Conte1, Floriana De Bellis1, Fabio Manzo1, Vincenzo Di Cerbo1, Rosaria Benedetti4, Loredana D'Amato1, Maria Marino25, Alessandro Bolli25, Giovanna Del Pozzo26, Nadia Diano236, Marianna Portaccio23, Gustavo D Mita34, Maria Teresa Vietri1, Michele Cioffi1, Ernesto Nola1, Carmela Dell'Aversana1, Vincenzo Sica1, Anna Maria Molinari1 and Lucia Altucci12*

Author Affiliations

1 Dipartimento di Patologia generale, Seconda Università di Napoli, Via L. De Crecchio 7 Napoli, Italy

2 Istituto Nazionale di Biostruttura e dei Biosistemi, Viale Medaglie d'Oro,305, 00100 Roma, Italy

3 Dipartimento di Medicina sperimentale, Seconda Università di Napoli, Via De Crecchio, Napoli, Italy

4 Dipartimento di Fisica, Università di Napoli 'Federico II', Napoli, Italy

5 Dipartimento di Biologia, Università Roma Tre, Viale Guglielmo Marconi 446, 00146 Roma, Italy

6 Istituto di Genetica e Biofisica del CNR, Via P. Castellino 111, 80100 Napoli, Italy

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Journal of Translational Medicine 2009, 7:48  doi:10.1186/1479-5876-7-48

Published: 18 June 2009

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.

Conclusion:

BPA is able to induce apoptosis in leukemia cells via caspase activation and involvement of both intrinsic and extrinsic pathways of apoptosis.