Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Department of Applied Chemistry, National Chi Nan University, Nantou, Taiwan.
Environ Toxicol. 2020 Dec;35(12):1386-1394. doi: 10.1002/tox.23003. Epub 2020 Jul 15.
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.
柚皮素（NGEN）是一种天然类黄酮，它对几种癌细胞具有生长抑制和诱导凋亡的作用。然而，NGEN 在肺癌细胞死亡中的细胞毒性机制尚未完全确定。在本研究中，NGEN 处理人肺腺癌细胞 A549 导致细胞活力呈时间和剂量依赖性下降。此外，NGEN 显著诱导细胞凋亡，表现为形态学变化、DAPI 染色、TUNEL 检测和亚 G1 期细胞群增加。在 NGEN 处理的细胞中，检测到 Bax 蛋白强烈上调和 Bcl-2 蛋白下调，并通过亚细胞分级分离分析 Bax 蛋白与线粒体膜的结合。用 shRNA 方法敲低 Bax 表达可显著保护 A549 细胞免受 NGEN 诱导的凋亡。用 caspase-3、-8 或 -9 的抑制剂处理可显著减少 NGEN 诱导的凋亡死亡。总之，我们的研究结果表明，NGEN 诱导的凋亡可能通过 Bax 激活的线粒体途径发生在肺腺癌细胞 A549 中。
