Naringenin-induced apoptosis via activation of NF-κB and necrosis involving the loss of ATP in human promyeloleukemia HL-60 cells
Naringenin-induced apoptosis via activation of NF-κB and necrosis involving the loss of ATP in human promyeloleukemia HL-60 cells
复制标题
DOI：
10.1016/j.toxlet.2006.06.005
复制
发表时间：
2006-10-10
影响因子：
3.5
通讯作者：
Ishikawa, Masaaki
中科院分区：
文献类型：
--
作者：
Kanno, Syu-ichi;Tomizawa, Ayako;Ishikawa, Masaaki
柚皮素 (NGEN) 是一种黄酮类化合物，在多种人类癌细胞系中表现出细胞毒性，并对肿瘤生长具有抑制作用。在本研究中，我们研究了 NGEN 通过激活 NF-κ B 诱导的细胞凋亡和涉及人早幼粒细胞白血病 HL-60 细胞中 ATP 丢失的坏死。暴露于 NGEN 会剂量依赖性地诱导细胞凋亡，直至 0.5 mM，但在 1 mM 时则不会，如核形态变化的定量分析和流式细胞术分析所证明的。一种广泛的半胱天冬酶抑制剂，可消除 NGEN 诱导的细胞凋亡。 NGEN的凋亡触发浓度显着促进caspase-3的激活，轻微促进caspase-9的激活，但对caspase-8没有影响。 NGEN 诱导的细胞凋亡是由特异性 NF-kappa B 结合活性的诱导引起的，并涉及 I kappa B α 的降解。与高浓度 NGEN (1 mM) 一起孵育会降低细胞内 ATP 水平，但在较低浓度下未观察到变化。 NGEN 增加线粒体膜电位的剂量依赖性超极化。该结果表明 NGEN 导致细胞凋亡和坏死的共同途径。 NGEN 诱导细胞凋亡的机制之一可能与 NF-κ B 的激活有关，而 NF-κ B 的激活与 I kappa B α 的降解相关。 NGEN 诱导坏死表明是由细胞内 ATP 耗竭和线粒体功能障碍引起的。 (c) 2006 Elsevier Ireland Ltd. 保留所有权利。
Naringenin (NGEN), a flavonoid, has shown cytotoxicity in various human cancer cell lines and inhibitory effects on tumor growth. In this study, we investigated the apoptosis induced by NGEN via the activation of NF-kappa B and necrosis involving the loss of ATP in human promyeloleukemia HL-60 cells. Exposure to NGEN induced apoptosis dose-dependently up until 0.5 mM, but not at I mM as demonstrated by a quantitative analysis of nuclear morphological change and flow cytometric analysis. An extensive inhibitor for caspases, abolished the NGEN-induced apoptosis. The apoptosis-triggering concentration of NGEN was shown to markedly promote the activation of caspase-3, and slightly promote that of caspase-9, but had no effect on caspase-8. NGEN-induced apoptosis caused by induction of specific NF-kappa B-binding activity and involving the degradation of I kappa B alpha. Incubation with a high concentration of NGEN (I mM) reduced intracellular ATP levels, but no change was observed at lower concentrations. NGEN increased dose-dependently hyperpolarization of mitochondrial membrane potential. This result indicates a common pathway to apoptosis and necrosis by NGEN. One of the mechanisms by NGEN-induced apoptosis may relate to the activation of NF-kappa B that correlates with degradation of I kappa B alpha. Induction of necrosis by NGEN suggests causing by intracellular ATP depletion and mitochondria dysfunctions. (c) 2006 Elsevier Ireland Ltd. All rights reserved.