Cargando…

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

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 activi...

Descripción completa

Detalles Bibliográficos
Autores principales: Yuan, Xiao-Long, Mao, Xin-Xin, Du, Yong-Mei, Yan, Pei-Zhen, Hou, Xiao-Dong, Zhang, Zhong-Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406568/
https://www.ncbi.nlm.nih.gov/pubmed/30696084
http://dx.doi.org/10.3390/biom9020045
_version_ 1783401340262678528
author Yuan, Xiao-Long
Mao, Xin-Xin
Du, Yong-Mei
Yan, Pei-Zhen
Hou, Xiao-Dong
Zhang, Zhong-Feng
author_facet Yuan, Xiao-Long
Mao, Xin-Xin
Du, Yong-Mei
Yan, Pei-Zhen
Hou, Xiao-Dong
Zhang, Zhong-Feng
author_sort Yuan, Xiao-Long
collection PubMed
description 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 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 N. tabacum L. can be potentially used as a natural antitumor agent.
format Online
Article
Text
id pubmed-6406568
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-64065682019-03-13 Anti-Tumor Activity of Cembranoid-Type Diterpenes Isolated from Nicotiana tabacum L. Yuan, Xiao-Long Mao, Xin-Xin Du, Yong-Mei Yan, Pei-Zhen Hou, Xiao-Dong Zhang, Zhong-Feng Biomolecules Article 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 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 N. tabacum L. can be potentially used as a natural antitumor agent. MDPI 2019-01-28 /pmc/articles/PMC6406568/ /pubmed/30696084 http://dx.doi.org/10.3390/biom9020045 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yuan, Xiao-Long
Mao, Xin-Xin
Du, Yong-Mei
Yan, Pei-Zhen
Hou, Xiao-Dong
Zhang, Zhong-Feng
Anti-Tumor Activity of Cembranoid-Type Diterpenes Isolated from Nicotiana tabacum L.
title Anti-Tumor Activity of Cembranoid-Type Diterpenes Isolated from Nicotiana tabacum L.
title_full Anti-Tumor Activity of Cembranoid-Type Diterpenes Isolated from Nicotiana tabacum L.
title_fullStr Anti-Tumor Activity of Cembranoid-Type Diterpenes Isolated from Nicotiana tabacum L.
title_full_unstemmed Anti-Tumor Activity of Cembranoid-Type Diterpenes Isolated from Nicotiana tabacum L.
title_short Anti-Tumor Activity of Cembranoid-Type Diterpenes Isolated from Nicotiana tabacum L.
title_sort anti-tumor activity of cembranoid-type diterpenes isolated from nicotiana tabacum l.
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406568/
https://www.ncbi.nlm.nih.gov/pubmed/30696084
http://dx.doi.org/10.3390/biom9020045
work_keys_str_mv AT yuanxiaolong antitumoractivityofcembranoidtypediterpenesisolatedfromnicotianatabacuml
AT maoxinxin antitumoractivityofcembranoidtypediterpenesisolatedfromnicotianatabacuml
AT duyongmei antitumoractivityofcembranoidtypediterpenesisolatedfromnicotianatabacuml
AT yanpeizhen antitumoractivityofcembranoidtypediterpenesisolatedfromnicotianatabacuml
AT houxiaodong antitumoractivityofcembranoidtypediterpenesisolatedfromnicotianatabacuml
AT zhangzhongfeng antitumoractivityofcembranoidtypediterpenesisolatedfromnicotianatabacuml