Anti-Tumor Activity of Cembranoid-Type Diterpenes Isolated from Nicotiana tabacum L.

文献类型： 外文期刊

第一作者： Yuan, Xiao-Long

作者： Yuan, Xiao-Long;Mao, Xin-Xin;Du, Yong-Mei;Yan, Pei-Zhen;Hou, Xiao-Dong;Zhang, Zhong-Feng

作者机构：

关键词： antitumor activity; alpha-cembratriene-diol; cytological observation; Nicotiana tabacum L.; transcriptome

期刊名称：BIOMOLECULES （ 影响因子：4.879； 五年影响因子：5.362 ）

ISSN： 2218-273X

年卷期： 2019 年 9 卷 2 期

页码：

收录情况： SCI

摘要： 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 Nicotiana tabacum L. and evaluated their antitumor activity against hepatoma cell lines. Particularly, the anti-tumor activity of alpha-2,7,11-cyprotermine-4,6-diol (alpha-CBD) was investigated against HepG2, SMMC-7721, and HL-7702 cells. The MTT assay revealed that alpha-CBD reduced the formation of cell clones and inhibited the proliferation of hepatocellular carcinoma cells. Morphological observations showed that alpha-CBD altered cell morphology and membrane permeability before inducing apoptosis. To further explore the antitumor mechanism of alpha-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 alpha-CBD inhibits the proliferation of hepatocellular carcinoma cells in the S phase. The gene expression analysis of HepG2 cells treated with alpha-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-kappa B-IAP pathways. Comprehensively, our study shows that alpha-CBD isolated from N. tabacum L. can be potentially used as a natural antitumor agent.

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