Molecular analysis of the apoptotic effects of BPA in acute myeloid leukemia cells
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
Journal of Translational Medicine 2009, 7:48 doi:10.1186/1479-5876-7-48Published: 18 June 2009
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.
Cell cycle, apoptosis and differentiation analyses; western blots.
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.
BPA is able to induce apoptosis in leukemia cells via caspase activation and involvement of both intrinsic and extrinsic pathways of apoptosis.