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

Molecular analysis of the apoptotic effects of BPA in acute myeloid leukemia cells.
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DOI:
10.1186/1479-5876-7-48
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发表时间:
2009-06-18
影响因子:
7.4
通讯作者:
Altucci L
Altucci L
中科院分区:
医学2区
文献类型:
--
作者:
Bontempo P;Mita L;Doto A;Miceli M;Nebbioso A;Lepore I;Franci G;Menafra R;Carafa V;Conte M;De Bellis F;Manzo F;Di Cerbo V;Benedetti R;D'Amato L;Marino M;Bolli A;Del Pozzo G;Diano N;Portaccio M;Mita GD;Vietri MT;Cioffi M;Nola E;Dell'aversana C;Sica V;Molinari AM;Altucci L

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BPA(双酚A或2,2-双(4-羟基苯酚)丙烷)存在于聚碳酸酯塑料和环氧树脂的制造中,可用于抗冲击安全设备和婴儿奶瓶,作为金属食品容器内的保护涂层,以及作为牙科的复合材料和密封剂。最近,人们的注意力集中在BPA的雌激素样和致癌副作用上。因此,有必要研究该化合物的细胞毒性和细胞毒性诱导活性。细胞周期、凋亡和分化分析;蛋白质印迹。BPA能够在三种不同的急性髓性白血病中诱导细胞周期停滞和凋亡。虽然一些粒细胞分化伴随发生在NB 4细胞BPA处理后,主要的行动是诱导细胞凋亡。BPA介导的细胞凋亡是半胱天冬酶依赖性的,通过激活调节FAS和TRAIL的外源性和内源性细胞死亡途径以及诱导NB 4细胞中BAD磷酸化而发生。最后,BPA还诱导了非基因组作用,例如ERK和AKT磷酸化的早期降低,从而表明BPA的凋亡作用发生了复杂的调控交叉。BPA能够通过半胱天冬酶激活和参与内源性和外源性凋亡途径诱导白血病细胞凋亡。
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.
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