Bruceine D induces apoptosis in human non-small cell lung cancer cells through regulating JNK pathway
Bruceine D induces apoptosis in human non-small cell lung cancer cells through regulating JNK pathway
复制标题
Bruceine D 通过调节 JNK 通路诱导人非小细胞肺癌细胞凋亡
DOI：
10.1016/j.biopha.2019.109089
复制
发表时间：
2019-09-01
影响因子：
7.5
通讯作者：
Lin, Nengming
中科院分区：
文献类型：
--
作者：
Tan, Biqin;Huang, Yuyu;Lin, Nengming
鸦胆子素D（Bruceine D，BD）是从中药鸦胆子果实中分离得到的苦木素类化合物，具有抗癌活性。在这里，我们证明了BD在体外抑制人非小细胞肺癌（NSCLC）细胞系，这归因于诱导细胞凋亡。用BD处理人NSCLC H460和A549细胞系，并用CCK-8测定法进行细胞活力测定。通过克隆形成试验观察细胞克隆形成。采用DAPI染色和流式细胞术检测细胞凋亡。通过蛋白质印迹分析蛋白质水平。结果表明，BD对H460和A549细胞活力的抑制作用呈剂量依赖性，作用48 h的IC 50值分别为0.5和0.6 μ mol/L。BD（0.125-1.0 μ mol/L）剂量依赖性地促进H460和A549细胞的染色质凝聚、Annexin V阳性细胞数和caspase依赖性凋亡。在机制上，BD刺激JNK的磷酸化。此外，在NSCLC细胞中，特异性JNK抑制剂SP 600125有效地减轻了BD的抗癌作用。综上所述，结果表明BD通过激活JNK对NSCLC细胞发挥抗癌活性，这表明其在预防和治疗NSCLC方面具有潜在的用途。
Bruceine D (BD) is the quassinoids isolated from the traditional Chinese herbal medicine Brucea javanica's fruit, which exhibits anti-cancer activity. Here, we demonstrated that BD inhibited human non-small cell lung cancer (NSCLC) cell lines in vitro that were attributed to the induction of cell apoptosis. Human NSCLC H460 and A549 cell lines were treated with BD, and cell viability was conducted with CCK-8 assay. Cell clone formation was observed by clone formation assay. Cell apoptosis was measured using DAPI staining and flow cytometry. Protein levels was analyzed by western blot. The results showed BD inhibited the cell viability of H460 and A549 cells in a dose-dependent manner with IC50 values of 0.5 and 0.6 mu mol/L, respectively, at 48 h of treatment. Treatment with BD (0.125-1.0 mu mol/L) dose-dependently promoted chromatin condensation, Annexin V-positive cell population and caspase-dependent apoptosis in H460 and A549 cells. Mechanistically, BD stimulated the phosphorylation of JNK. Furthermore, the anti-cancer effects of BD were alleviated effectively by a specific JNK inhibitor SP600125 in NSCLC cells. In conclusion, the results demonstrated that BD exerted anti-cancer activity against NSCLC cells through JNK activation, which suggests its potent usefulness for prevention and treatment of NSCLC.