Licochalcone A-induced human gastric cancer BGC-823 cells apoptosis by regulating ROS-mediated MAPKs and PI3K/AKT signaling pathways.

Licochalcone A-induced human gastric cancer BGC-823 cells apoptosis by regulating ROS-mediated MAPKs and PI3K/AKT signaling pathways.
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甘草查耳酮 A 通过调节 ROS 介导的 MAPKs 和 PI3K/AKT 信号通路诱导人胃癌 BGC-823 细胞凋亡

DOI:
10.1038/srep10336
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发表时间:
2015-05-18
期刊:
影响因子:
4.6
通讯作者:
Zheng Q
Zheng Q
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hao W;Yuan X;Yu L;Gao C;Sun X;Wang D;Zheng Q

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磷脂酰肌醇3-激酶(PI 3 K)/AKT和丝裂原活化蛋白激酶(MAPK)信号通路在肿瘤细胞的增殖、存活、血管生成和转移中起重要作用。本研究探讨甘草黄酮类化合物甘草查尔酮A(LA)对人胃癌BGC-823细胞中PI 3 K/AKT/mTOR和MAPK激活通路的影响。LA增加了活性氧(ROS)水平,这与凋亡的诱导有关,其特征在于阳性膜联蛋白V结合和caspase-3的激活以及聚ADP-核糖聚合酶(PARP)的裂解。N-乙酰半胱氨酸(NAC)抑制活性氧的产生显着防止LA诱导的细胞凋亡。有趣的是,我们还观察到LA引起BGC-823细胞中ERK、JNK和p38 MAPK的激活。LA处理的BGC-823细胞在KM小鼠体内具有明显的抗肿瘤活性。我们的研究结果表明,LA可以干扰MAPK信号级联,启动ROS的产生,诱导氧化应激,从而导致BGC细胞凋亡。
Both phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen activated protein kinase (MAPK) signaling cascades play an important role in cell proliferation, survival, angiogenesis and metastasis of tumor cells. In the present report, we investigated the effects of licochalcone A (LA), a flavonoid extracted from licorice root, on the PI3K/AKT/mTOR and MAPK activation pathways in human gastric cancer BGC-823 cells. LA increased reactive oxygen species (ROS) levels, which is associated with the induction of apoptosis as characterized by positive Annexin V binding and activation of caspase-3 and cleavage of poly-ADP-ribose polymerase (PARP). Inhibition of ROS generation by N-acetylcysteine (NAC) significantly prevented LA-induced apoptosis. Interestingly, we also observed that LA caused the activation of ERK, JNK and p38 MAPK in BGC-823 cells. The antitumour activity of LA-treated BGC-823 cells was significantly distinct in KM micein vivo. All the findings from our study suggest that LA can interfere with MAPK signaling cascades, initiate ROS generation, induce oxidative stress and consequently cause BGC cell apoptosis.
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