Punicalagin induces ROS-mediated apoptotic cell death through inhibiting STAT3 translocation in lung cancer A549 cells

Punicalagin induces ROS-mediated apoptotic cell death through inhibiting STAT3 translocation in lung cancer A549 cells
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DOI:
10.1002/jbt.22771
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发表时间:
2021-03-15
影响因子:
3.6
通讯作者:
Fang, Xiaolei
Fang, Xiaolei
中科院分区:
医学4区
文献类型:
--
作者:
Fang, Le;Wang, Hong;Fang, Xiaolei

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肺癌是一种总生存期不达标的有害疾病。尽管如此,有几种治疗肺癌的策略包括化疗,放疗,手术;然而,总体存活率仍然很低。槟榔苷已被证明是一种潜在的植物药,可以选择性地抑制许多癌症的进展和扩张。在本研究中,我们通过抑制STAT-3的激活诱导凋亡,来评估槟榔苷对肺癌A549细胞的抗增殖能力。Punicalagin在24 h后诱导A549细胞的毒性作用呈剂量相关。我们还观察到punicalagin(10、20和30 μ M)诱导活性氧生成,改变线粒体膜电位和凋亡形态学改变。stat3过表达调节细胞凋亡、增殖和血管生成。在A549细胞中,punicalagin通过抑制Bcl-2的表达和增强Bax、细胞色素c、caspase-9和caspase-3的表达,抑制STAT-3易位,从而诱导细胞凋亡。因此,我们认为punicalagin是一种治疗非小细胞肺恶性肿瘤的可能方法。总之,槟榔苷是一种很有前途的治疗恶性肿瘤的植物药物,需要进一步的努力来揭示其全部潜力。
Lung cancer is a noxious disease with substandard overall survival. Despite this, there are several treatment strategies for lung cancer include chemotherapy, radiotherapy, surgery; however, the overall survival remains poor. Punicalagin has been documented as a potential phytomedicine to selectively inhibit the progression and expansion of numerous cancers. In the present study, we evaluated the antiproliferative ability of punicalagin against lung cancer A549 cells by inducing apoptosis by inhibiting STAT-3 activation. Punicalagin induces toxic effects of A549 cells in a dose-associated manner after 24 h treatment. And we also observed that punicalagin (10, 20, and 30 mu M) induced reactive oxygen species generation, alters the mitochondrion membrane potential and apoptotic morphological changes in A549 cells. The STAT-3 overexpression regulates apoptosis, proliferation, and angiogenesis. Here, the punicalagin inhibited STAT-3 translocation and thereby induces apoptosis by inhibiting expression Bcl-2 and enhanced expression of Bax, cytochrome-c, caspase-9, and caspase-3 in A549 cells. Hence, we stated that the punicalagin is a possible therapy for non-small cell lung, malignancies. Altogether, the punicalagin is a promising phytomedicine in malignancy treatment and further endeavors are needed to unveil the complete potential.