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.

中文翻译：

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Scutebarbatine A通过激活MAPK和ER应激信号通路诱导肝癌的细胞毒性

Scutebarbatine A（SBT-A），在半枝黄the的根中发现的一种二萜类生物碱D. Don，据报道可诱导A549细胞凋亡。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潜在机制。我们的结果表明，SBT-A以剂量依赖的方式抑制HCC细胞的生长。SBT-A处理导致细胞周期停滞，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通过半胱天冬酶依赖性途径触发细胞凋亡，通过泛半胱天冬酶抑制剂Z-VAD-FMK预处理可部分恢复细胞活力。在HCC细胞中，用SBT-A处理可增加细胞外信号调节激酶1和2（ERK1 / 2），c-Jun N端激酶1和2（JNK1 / 2）和p38促分裂原活化蛋白激酶的磷酸化（p38 MAPK）。而且，SBT‐A通过上调蛋白激酶RNA样ER激酶（PERK），激活转录因子4（ATF-4）和CCAAT增强子结合蛋白（C / EBP）同源蛋白来激活内质网（ER）应激（劈）。我们的数据表明SBT-A通过激活MAPK和ER应激来抑制HCC细胞的增殖并触发其凋亡。SBT‐A是治疗HCC的潜在药物。