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.

中文翻译：

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柚皮素的细胞毒性诱导人肺腺癌 A549 细胞中 Bax 介导的线粒体凋亡

柚皮素 (NGEN) 是一种天然黄酮类化合物，在多种癌细胞中具有生长抑制和凋亡诱导活性。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，用 NGEN 治疗人肺腺癌细胞 A549 导致细胞活力的时间和剂量依赖性降低。此外，通过形态学变化、DAPI 染色、TUNEL 测定和亚 G1 种群增加，NGEN 显着诱导细胞凋亡。在 NGEN 处理的细胞中，检测到强烈上调的 Bax 和下调的 Bcl-2 蛋白，并通过亚细胞分级分析与线粒体膜相关的 Bax 蛋白。通过 shRNA 方法抑制 Bax 表达显着保护 A549 细胞免受 NGEN 诱导的细胞凋亡。用 caspase-3、-8 或 -9 抑制剂治疗显着减少了 NGEN 诱导的细胞凋亡。总之，我们的结果表明 NGEN 诱导的细胞凋亡可能通过肺腺癌 A549 细胞中的 Bax 激活的线粒体途径发生。