Scutebarbatine A induces cytotoxicity in hepatocellular carcinoma via activation of the MAPK and ER stress signaling pathways
Scutebarbatine A induces cytotoxicity in hepatocellular carcinoma via activation of the MAPK and ER stress signaling pathways
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Scutebarbatine A 通过激活 MAPK 和 ER 应激信号通路诱导肝细胞癌的细胞毒性
DOI：
10.1002/jbt.22731
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发表时间：
2021-01-29
影响因子：
3.6
通讯作者：
Fei, Hong-rong
中科院分区：
文献类型：
--
作者：
Feng, Pan-pan;Qi, You-kun;Fei, Hong-rong
黄芩碱A （Scutebarbatine A, stt -A）是一种在黄芩根中发现的二萜类生物碱，具有诱导A549细胞凋亡的作用。在这项研究中，我们研究了SBT-A在人肝细胞癌（HCC）细胞中的抗肿瘤活性及其潜在的机制。我们的研究结果显示，SBT-A以剂量依赖的方式抑制HCC细胞的生长。SBT-A处理导致细胞周期阻滞，并降低细胞周期蛋白B1、细胞周期蛋白D1、p-Cdc2和p-Cdc25C的表达。SBT-A通过caspase依赖途径触发细胞凋亡，并通过泛caspase抑制剂Z-VAD-FMK预处理部分恢复细胞活力。在HCC细胞中，stt -a处理增加了细胞外信号调节激酶1和2 （ERK1/2）、c-Jun n末端激酶1和2 （JNK1/2）和p38丝裂原活化蛋白激酶（p38 MAPK）的磷酸化。此外，SBT-A通过上调蛋白激酶rna样ER激酶（PERK）、活化转录因子4 （ATF-4）和ccaat增强子结合蛋白（C/EBP）同源蛋白（CHOP）激活内质网（ER）应激。我们的数据表明，SBT-A通过激活MAPK和内质网应激来抑制HCC细胞的增殖并触发其凋亡。SBT-A是一种治疗HCC的潜在药物。
Scutebarbatine A (SBT-A), a diterpenoid alkaloid found in the root of Scutellaria barbata D. Don, has been reported to induce the apoptosis of A549 cells. In this study, we investigated the antitumor activity of SBT-A in human hepatocellular carcinoma (HCC) cells and the potential underlying mechanisms. Our results showed that SBT-A inhibited the growth of HCC cells in a dose-dependent manner. SBT-A treatment caused cell cycle arrest and decreased the expression of cyclin B1, cyclin D1, p-Cdc2, and p-Cdc25C. SBT-A triggered cell apoptosis via a caspase-dependent pathway, and cell viability was partially restored by pretreatment with the pan-caspase inhibitor Z-VAD-FMK. In HCC cells, treatment with SBT-A increased the phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2), c-Jun N-terminal kinase 1 and 2 (JNK1/2), and p38 mitogen-activated protein kinase (p38 MAPK). Moreover, SBT-A activated endoplasmic reticulum (ER) stress through the upregulation of protein kinase RNA-like ER kinase (PERK), activating transcription factor 4 (ATF-4), and CCAAT-enhancer-binding protein (C/EBP) homologous protein (CHOP). Our data indicate that SBT-A inhibits the proliferation of HCC cells and triggers their apoptosis via the activation of MAPK and ER stress. SBT-A is a potential agent for the treatment of HCC.