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

In vitro Cytotoxicity of Bisphenol A in Monocytes Cell Line

“…At particularly low BPA concentrations, the cellular cytotoxic (in vitro) effects are immediately evident, suggesting a very strong in vitro association. Unlike the behavior of other cell cultures influenced by BPA doses described in literature [29,30] , our in vitro study showed that the concentrations at which viability of monocytes start to decrease, and necrosis and apoptosis of monocytes start to increase, are lower. We hypothesize that this fact may be explainable by 2 reasons: (i) primarily, a blood cell culture like U937 is very susceptible to increasing BPA concentrations in terms of cytotoxic effects; (ii) secondarily, the results deriving from the in vitro setup overestimates the real in vivo cytotoxic effect of BPA.…”

“…Thus, it becomes essential to investigate the cytotoxicity and apoptosis-inducing activities of BPA at the molecular level, especially in blood components. It has already been reported that the human exposure to BPA leads to potential cytotoxic activity against different human cell cultures [29,30] , but unfortunately no studies have considered blood cells.…”

Low dose bisphenol A impairs spermatogenesis by suppressing reproductive hormone production and promoting germ cell apoptosis in adult rats

“…A recent in vitro study has revealed the cytotoxicity of low dose BPA through the up-regulation of Bax and the down-regulation of Bcl-2[35]. Additionally, BPA-induced apoptotic cell death is known to be through calcium-mediated oxidative stress in HT-22 cells[36] and decreasing ERK and Akt phosphorylation in acute myeloid leukemia cells[37]. Moreover, BPA-induced impairment of Sertoli cells has been reported by inhibiting endoplasmic reticulum Ca 2+ homeostasis[38],[39] and the ectoplasmic specialization between Sertoli cells and spermatids[40].…”

Biodegradation of Phenol and Phenolic Derivatives by a Mixture of Immobilized Cells ofAspergillus AwamoriandTrichosporon Cutaneum

“…it was recently shown that a relatively small number of phenols show estrogenic activity. to this group belong biphenyls, hydroxybiphenyls, some chlorophenols (9,30).…”