Theabrownin Inhibits Cell Cycle Progression and Tumor Growth of Lung Carcinoma through c-myc-Related Mechanism

Publication type:

Journal article

Metadata:

Autoren

Li Zhou
Feifei Wu
Wangdong Jin
Bo Yan
Xin Chen
Yingfei He
Weiji Yang
Wenlin Du
Qiang Zhang
Yonghua Guo
Qiang Yuan
Xiaoqiao Dong
Wenhua Yu
Jin Zhang
Luwei Xiao
Peijian Tong
Letian Shan
Thomas Efferth

Autoren-URL

https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000394743800001&DestLinkType=FullRecord&DestApp=WOS_CPL

DOI

10.3389/fphar.2017.00075

eISSN

1663-9812

Externe Identifier

Clarivate Analytics Document Solution ID: EL6PF
PubMed Identifier: 28289384

Zeitschrift

FRONTIERS IN PHARMACOLOGY

Schlüsselwörter

theabrownin
lung cancer
TUNEL
cell cycle
c-myc

Artikelnummer

ARTN 75

Paginierung

1 - 10

Datum der Veröffentlichung

2017

Status

Published

Titel

Theabrownin Inhibits Cell Cycle Progression and Tumor Growth of Lung Carcinoma through c-myc-Related Mechanism

Sub types

Article

Ausgabe der Zeitschrift

Data source: Web of Science (Lite)

Other metadata sources:

Autoren

Li Zhou
Feifei Wu
Wangdong Jin
Bo Yan
Xin Chen
Yingfei He
Weiji Yang
Wenlin Du
Qiang Zhang
Yonghua Guo
Qiang Yuan
Xiaoqiao Dong
Wenhua Yu
Jin Zhang
Luwei Xiao
Peijian Tong
Letian Shan
Thomas Efferth

DOI

10.3389/fphar.2017.00075

eISSN

1663-9812

Zeitschrift

Frontiers in Pharmacology

Online publication date

2017

Status

Published online

Herausgeber

Frontiers Media SA

Herausgeber URL

http://dx.doi.org/10.3389/fphar.2017.00075

Datum der Datenerfassung

2019

Titel

Theabrownin Inhibits Cell Cycle Progression and Tumor Growth of Lung Carcinoma through c-myc-Related Mechanism

Ausgabe der Zeitschrift

Data source: Crossref

Abstract

Green tea, the fresh leaves of Camellia sinensis, is not only a health-promoting beverage but also a traditional Chinese medicine used for prevention or treatment of cancer, such as lung cancer. Theabrownin (TB) is the main fraction responsible for the medicinal effects of green tea, but whether it possesses anti-cancer effect is unknown yet. This study aimed to determine the in vitro and in vivo anti-lung cancer effect of TB and explore the underlying molecular mechanism, by using A549 cell line and Lewis lung carcinoma-bearing mice. In cellular experiment, MTT assay was performed to evaluate the inhibitory effect and IC50 values of TB, and flow cytometry was conducted to analyze the cell cycle progression affected by TB. In animal experiment, mice body mass, tumor incidence, tumor size and tumor weight were measured, and histopathological analysis on tumor was performed with Transferase dUTP nick-end labeling staining. Real time PCR and western blot assays were adopted to detect the expression of C-MYC associated genes and proteins for mechanism clarification. TB was found to inhibit A549 cell viability in a dose- and time-dependent manner and block A549 cell cycle at G0/G1 phase. Down-regulation of c-myc, cyclin A, cyclin D, cdk2, cdk4, proliferation of cell nuclear antigen and up-regulation of p21, p27, and phosphate and tension homolog in both gene and protein levels were observed with TB treatment. A c-myc-related mechanism was thereby proposed, since c-myc could transcriptionally regulate all other genes in its downstream region for G1/S transitions of cell cycle and proliferation of cancer cells. This is the first report regarding the anti-NSCLC effect and the underlying mechanism of TB on cell cycle progression and proliferation of A549 cells. The in vivo data verified the in vitro result that TB could significantly inhibit the lung cancer growth in mice and induce apoptosis on tumors in a dose-dependent manner. It provides a promising candidate of natural products for lung cancer therapy and new development of anti-cancer agent.

Addresses

Institute of Orthopaedics and Traumatology, Zhejiang Chinese Medical University Hangzhou, China.

Autoren

Li Zhou
Feifei Wu
Wangdong Jin
Bo Yan
Xin Chen
Yingfei He
Weiji Yang
Wenlin Du
Qiang Zhang
Yonghua Guo
Qiang Yuan
Xiaoqiao Dong
Wenhua Yu
Jin Zhang
Luwei Xiao
Peijian Tong
Letian Shan
Thomas Efferth
Thomas Efferth

DOI

10.3389/fphar.2017.00075

eISSN

1663-9812

Externe Identifier

PubMed Identifier: 28289384
PubMed Central ID: PMC5326752

Funding acknowledgements

Zhejiang Chinese Medical University: 2013ZY23
National Natural Science Foundation of China: 81302989

Open access

true

ISSN

1663-9812

Zeitschrift

Frontiers in pharmacology

Sprache

eng

Medium

Electronic-eCollection

Online publication date

2017

Open access status

Open Access

Paginierung

Datum der Veröffentlichung

2017

Status

Published

Publisher licence

CC BY

Datum der Datenerfassung

2017

Titel

Theabrownin Inhibits Cell Cycle Progression and Tumor Growth of Lung Carcinoma through c-myc-Related Mechanism.

Sub types

research-article
Journal Article

Ausgabe der Zeitschrift

Files

https://www.frontiersin.org/articles/10.3389/fphar.2017.00075/pdf https://europepmc.org/articles/PMC5326752?pdf=render

Data source: Europe PubMed Central

Abstract

Green tea, the fresh leaves of Camellia sinensis, is not only a health-promoting beverage but also a traditional Chinese medicine used for prevention or treatment of cancer, such as lung cancer. Theabrownin (TB) is the main fraction responsible for the medicinal effects of green tea, but whether it possesses anti-cancer effect is unknown yet. This study aimed to determine the in vitro and in vivo anti-lung cancer effect of TB and explore the underlying molecular mechanism, by using A549 cell line and Lewis lung carcinoma-bearing mice. In cellular experiment, MTT assay was performed to evaluate the inhibitory effect and IC50 values of TB, and flow cytometry was conducted to analyze the cell cycle progression affected by TB. In animal experiment, mice body mass, tumor incidence, tumor size and tumor weight were measured, and histopathological analysis on tumor was performed with Transferase dUTP nick-end labeling staining. Real time PCR and western blot assays were adopted to detect the expression of C-MYC associated genes and proteins for mechanism clarification. TB was found to inhibit A549 cell viability in a dose- and time-dependent manner and block A549 cell cycle at G0/G1 phase. Down-regulation of c-myc, cyclin A, cyclin D, cdk2, cdk4, proliferation of cell nuclear antigen and up-regulation of p21, p27, and phosphate and tension homolog in both gene and protein levels were observed with TB treatment. A c-myc-related mechanism was thereby proposed, since c-myc could transcriptionally regulate all other genes in its downstream region for G1/S transitions of cell cycle and proliferation of cancer cells. This is the first report regarding the anti-NSCLC effect and the underlying mechanism of TB on cell cycle progression and proliferation of A549 cells. The in vivo data verified the in vitro result that TB could significantly inhibit the lung cancer growth in mice and induce apoptosis on tumors in a dose-dependent manner. It provides a promising candidate of natural products for lung cancer therapy and new development of anti-cancer agent.

Date of acceptance

2017

Autoren

Li Zhou
Feifei Wu
Wangdong Jin
Bo Yan
Xin Chen
Yingfei He
Weiji Yang
Wenlin Du
Qiang Zhang
Yonghua Guo
Qiang Yuan
Xiaoqiao Dong
Wenhua Yu
Jin Zhang
Luwei Xiao
Peijian Tong
Letian Shan
Thomas Efferth

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/28289384

DOI

10.3389/fphar.2017.00075

Externe Identifier

PubMed Central ID: PMC5326752

ISSN

1663-9812

Zeitschrift

Front Pharmacol

Schlüsselwörter

TUNEL
c-myc
cell cycle
lung cancer
theabrownin

Sprache

eng

Country

Switzerland

Paginierung

Datum der Veröffentlichung

2017

Status

Published online

Titel

Theabrownin Inhibits Cell Cycle Progression and Tumor Growth of Lung Carcinoma through c-myc-Related Mechanism.

Sub types

Journal Article

Ausgabe der Zeitschrift

Data source: PubMed

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Pharmazeutische Biologie

Theabrownin Inhibits Cell Cycle Progression and Tumor Growth of Lung Carcinoma through c-myc-Related Mechanism

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