| Molecular analysis of the apoptotic effects of BPA in acute myeloid leukemia cells. | |
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MedLine Citation:
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PMID: 19538739 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Paola Bontempo; Luigi Mita; Antonella Doto; Marco Miceli; Angela Nebbioso; Ilaria Lepore; GianLuigi Franci; Roberta Menafra; Vincenzo Carafa; Mariarosaria Conte; Floriana De Bellis; Fabio Manzo; Vincenzo Di Cerbo; Rosaria Benedetti; Loredana D'Amato; Maria Marino; Alessandro Bolli; Giovanna Del Pozzo; Nadia Diano; Marianna Portaccio; Gustavo D Mita; Maria Teresa Vietri; Michele Cioffi; Ernesto Nola; Carmela Dell'aversana; Vincenzo Sica; Anna Maria Molinari; Lucia Altucci |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-06-18 |
Journal Detail:
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Title: Journal of translational medicine Volume: 7 ISSN: 1479-5876 ISO Abbreviation: J Transl Med Publication Date: 2009 |
Date Detail:
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Created Date: 2009-07-29 Completed Date: 2009-11-04 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 101190741 Medline TA: J Transl Med Country: England |
Other Details:
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Languages: eng Pagination: 48 Citation Subset: IM |
Affiliation:
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Dipartimento di Patologia generale, Seconda Università di Napoli, Via L, De Crecchio 7, Napoli, Italy. paola.bontempo@unina2.it |
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| MeSH Terms | |
Descriptor/Qualifier:
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Antigens, CD11c
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metabolism Antigens, CD95 / metabolism Apoptosis / drug effects* Caspases / metabolism Cell Death / drug effects Cell Differentiation / drug effects Dose-Response Relationship, Drug Enzyme Activation / drug effects Extracellular Signal-Regulated MAP Kinases / metabolism Free Radical Scavengers / pharmacology* HL-60 Cells Humans Leukemia, Myeloid, Acute / genetics, metabolism, pathology* Phenols / pharmacology* Phosphorylation / drug effects Proto-Oncogene Proteins c-akt / metabolism TNF-Related Apoptosis-Inducing Ligand / metabolism Time Factors Tumor Cells, Cultured bcl-Associated Death Protein / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD11c; 0/Antigens, CD95; 0/BAD protein, human; 0/Free Radical Scavengers; 0/Phenols; 0/TNF-Related Apoptosis-Inducing Ligand; 0/bcl-Associated Death Protein; 80-05-7/bisphenol A; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 3.4.22.-/Caspases |
| Comments/Corrections | |
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