Department of Biochemistry and Molecular Biology, Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China.
Int J Mol Med. 2018 Jan;41(1):464-472. doi: 10.3892/ijmm.2017.3250. Epub 2017 Nov 9.
Lung cancer has high incidence and mortality rates worldwide. In the present study, the mechanisms by which hesperidin decreases the viability and induces the apoptosis of human non-small cell lung cancer (NSCLC) A549 cells were investigated. Initially, MTT and flow cytometric assays were performed to evaluate the effects of hesperidin on the viability and apoptosis of A549 cells and human normal lung epithelial BEAS-2B cells. The results revealed that hesperidin has no negative effects on the human normal lung epithelial BEAS-2B cells and the viability of cells treated with various concentrations of hesperidin was inhibited in a time- and dose-dependent manner compared with the control groups. Subsequently, the expression levels of proteins involved in the mitochondria-associated apoptotic pathway were studied by western blot analysis. Hesperidin was identified to induce A549 cell apoptosis by downregulating the levels of B-cell lymphoma-2 (Bcl-2) and Bcl extra large protein and simultaneously upregulating the levels of Bcl-2-associated X protein, BH3 interacting-domain death agonist (Bid), tBid, cleaved caspase-9, cleaved caspase-3 and cleaved poly(adenosine diphosphate ribose)polymerase. The effect of hesperidin on the cell cycle was assessed by flow cytometry. Hesperidin was observed to cause G0/G1 arrest of A549 cells by decreasing the expression of cyclin D1 and increasing the expression of p21 and p53. In summary, it was demonstrated that hesperidin induced apoptosis through the mitochondrial apoptotic pathway and induced G0/G1 arrest in human NSCLC A549 cells. Therefore, hesperidin may be developed as a potential therapeutic drug for the treatment of NSCLC.
肺癌在全球范围内具有较高的发病率和死亡率。本研究旨在探讨橙皮苷降低人非小细胞肺癌（NSCLC）A549 细胞活力和诱导细胞凋亡的机制。首先，通过 MTT 和流式细胞术检测橙皮苷对 A549 细胞和人正常肺上皮 BEAS-2B 细胞活力和凋亡的影响。结果表明，橙皮苷对人正常肺上皮 BEAS-2B 细胞无不良影响，且与对照组相比，用不同浓度橙皮苷处理的细胞活力呈时间和剂量依赖性抑制。随后，通过 Western blot 分析研究了线粒体相关凋亡途径中蛋白的表达水平。橙皮苷通过下调 B 细胞淋巴瘤-2（Bcl-2）和 Bcl 额外大蛋白的水平，并同时上调 Bcl-2 相关 X 蛋白、BH3 相互作用域死亡激动剂（Bid）、tBid、裂解的胱天蛋白酶-9、裂解的胱天蛋白酶-3 和裂解的多聚（腺苷二磷酸核糖）聚合酶，诱导 A549 细胞凋亡。通过流式细胞术评估橙皮苷对细胞周期的影响。橙皮苷通过降低 cyclin D1 的表达和增加 p21 和 p53 的表达，导致 A549 细胞 G0/G1 期阻滞。综上所述，橙皮苷通过线粒体凋亡途径诱导人 NSCLC A549 细胞凋亡，并诱导 G0/G1 期阻滞。因此，橙皮苷可能被开发为治疗 NSCLC 的潜在治疗药物。
