Tobacco Research Institute of Chinese Academy of Agricultural Sciences, Qingdao 266101, China.
Biomolecules. 2019 Jan 28;9(2):45. doi: 10.3390/biom9020045.
Recently, the incidence of hepatocellular carcinoma has increased worldwide. Cembranoid-type diterpenes (CBDs) from tobacco exhibit good antimicrobial, antitumor, and neuroprotective activities. Therefore, in this study, we isolated CBDs from L. and evaluated their antitumor activity against hepatoma cell lines. Particularly, the anti-tumor activity of α-2,7,11-cyprotermine-4,6-diol (α-CBD) was investigated against HepG2, SMMC-7721, and HL-7702 cells. The MTT assay revealed that α-CBD reduced the formation of cell clones and inhibited the proliferation of hepatocellular carcinoma cells. Morphological observations showed that α-CBD altered cell morphology and membrane permeability before inducing apoptosis. To further explore the antitumor mechanism of α-CBD, flow cytometry and transcriptome analysis were performed using HepG2 cells. The results showed that the number of HepG2 cells increased from 10.4% to 29.8%, indicating that α-CBD inhibits the proliferation of hepatocellular carcinoma cells in the S phase. The gene expression analysis of HepG2 cells treated with α-CBD showed 3068 genes with altered expression, among which 1289 were upregulated and 1779 were downregulated. Apoptosis induced by these differentially expressed genes might be mediated by the p53-PUMA, PI3K-Akt, and IL-1-NF-κB-IAP pathways. Comprehensively, our study shows that α-CBD isolated from L. can be potentially used as a natural antitumor agent.
最近，全球范围内肝细胞癌的发病率有所增加。烟草中的贝壳杉烷型二萜（CBDs）具有良好的抗菌、抗肿瘤和神经保护活性。因此，在本研究中，我们从 L. 中分离出 CBDs，并评估其对肝癌细胞系的抗肿瘤活性。特别是，研究了 α-2,7,11-环丙啶-4,6-二醇（α-CBD）对 HepG2、SMMC-7721 和 HL-7702 细胞的抗肿瘤活性。MTT 测定显示，α-CBD 减少细胞克隆的形成并抑制肝癌细胞的增殖。形态学观察表明，α-CBD 在诱导细胞凋亡之前改变了细胞形态和膜通透性。为了进一步探讨 α-CBD 的抗肿瘤机制，我们使用 HepG2 细胞进行了流式细胞术和转录组分析。结果表明，HepG2 细胞的数量从 10.4%增加到 29.8%，表明 α-CBD 抑制了 S 期肝癌细胞的增殖。用 α-CBD 处理的 HepG2 细胞的基因表达分析显示，有 3068 个基因的表达发生了改变，其中 1289 个基因上调，1779 个基因下调。这些差异表达基因诱导的细胞凋亡可能通过 p53-PUMA、PI3K-Akt 和 IL-1-NF-κB-IAP 途径介导。综上所述，我们的研究表明，从 L. 中分离出的 α-CBD 可能可作为一种天然的抗肿瘤药物。
