Cytotoxicity of naringenin induces Bax-mediated mitochondrial apoptosis in human lung adenocarcinoma A549 cells.
Cytotoxicity of naringenin induces Bax-mediated mitochondrial apoptosis in human lung adenocarcinoma A549 cells.
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DOI：
10.1002/tox.23003
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发表时间：
2020-12
影响因子：
4.5
通讯作者：
Cherng SH
中科院分区：
文献类型：
--
作者：
Lu WL;Yu CR;Lien HM;Sheu GT;Cherng SH
柚皮苷元是一种天然的黄酮类化合物，对多种肿瘤细胞具有生长抑制和诱导凋亡活性。然而，NGEN在肺癌细胞死亡中的细胞毒作用机制尚未完全明确。在本研究中，人肺腺癌A549细胞经NGEN处理后，细胞存活率呈时间和剂量依赖性下降。此外，从细胞形态、DAPI染色、TUNEL检测和亚G1期细胞数量的增加可以看出，NGEN显著诱导了细胞的凋亡。在NGEN处理的细胞中，检测到Bax蛋白表达上调，而Bcl2蛋白表达下调，并通过亚细胞分离分析与线粒体膜相关的Bax蛋白。通过shRNA方法抑制Bax的表达可显著保护A549细胞免受ngen诱导的细胞凋亡。用caspase-3、-8或-9的抑制剂治疗可显著减少ngen诱导的细胞凋亡死亡。综上所述，我们的结果表明，ngen可能通过Bax激活的线粒体途径诱导肺腺癌A549细胞发生凋亡。
Naringenin (NGEN), a natural flavonoid has growth inhibition and apoptosis‐inducing activities in several cancer cells. However, the cytotoxicity mechanisms of NGEN in cell death of lung cancer cells have not been fully defined. In present study, treatment of human lung adenocarcinoma A549 cells with NGEN resulted in time‐ and dose‐dependent decreases in cell viability. Moreover, NGEN significantly induced apoptosis evidenced by morphological changes, DAPI staining, TUNEL assay and sub‐G1 population increase. In NGEN‐treated cells, intensely upregulated Bax and down‐regulated Bcl‐2 proteins were detected and the Bax protein associated with the mitochondrial membrane was analyzed by subcellular fractionation. Knockdown of the Bax expression by the shRNA method dramatically protected A549 cells against NGEN‐induced apoptosis. Treatment with the inhibitors of caspase‐3, ‐8, or ‐9 significantly reduced NGEN‐induced apoptotic deaths. Taken together, our results demonstrate that NGEN‐induced apoptosis may occur via a Bax‐activated mitochondrial pathway in lung adenocarcinoma A549 cells.
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