Anti-Proliferative and Apoptosis-Inducing Effect of Theabrownin against Non-small Cell Lung Adenocarcinoma A549 Cells

Publication type:

Journal article

Metadata:

Autoren

Feifei Wu
Li Zhou
Wangdong Jin
Weiji Yang
Ying Wang
Bo Yan
Wenlin Du
Qiang Zhang
Lei Zhang
Yonghua Guo
Jin Zhang
Letian Shan
Thomas Efferth

Autoren-URL

https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000389076700001&DestLinkType=FullRecord&DestApp=WOS_CPL

DOI

10.3389/fphar.2016.00465

Externe Identifier

Clarivate Analytics Document Solution ID: ED7UJ
PubMed Identifier: 27994550

ISSN

1663-9812

Zeitschrift

FRONTIERS IN PHARMACOLOGY

Schlüsselwörter

lung cancer
A549 cells
theabrownin
apoptosis
P53

Artikelnummer

ARTN 465

Datum der Veröffentlichung

2016

Status

Published

Titel

Anti-Proliferative and Apoptosis-Inducing Effect of Theabrownin against Non-small Cell Lung Adenocarcinoma A549 Cells

Sub types

Article

Ausgabe der Zeitschrift

Data source: Web of Science (Lite)

Other metadata sources:

Autoren

Feifei Wu
Li Zhou
Wangdong Jin
Weiji Yang
Ying Wang
Bo Yan
Wenlin Du
Qiang Zhang
Lei Zhang
Yonghua Guo
Jin Zhang
Letian Shan
Thomas Efferth

DOI

10.3389/fphar.2016.00465

eISSN

1663-9812

Zeitschrift

Frontiers in Pharmacology

Online publication date

2016

Status

Published online

Herausgeber

Frontiers Media SA

Herausgeber URL

http://dx.doi.org/10.3389/fphar.2016.00465

Datum der Datenerfassung

2019

Titel

Anti-Proliferative and Apoptosis-Inducing Effect of Theabrownin against Non-small Cell Lung Adenocarcinoma A549 Cells

Ausgabe der Zeitschrift

Data source: Crossref

Abstract

With the highest cancer incidence rate, lung cancer, especially non-small cell lung cancer (NSCLC), is the leading cause of cancer death in the world. Tea (leaves of Camellia sinensis) has been widely used as a traditional beverage beneficial to human health, including anti-NSCLC activity. Theabrownin (TB) is one major kind of tea pigment responsible for the beneficial effects of tea liquor. However, its effect on NSCLC is unknown. The aim of the present study was to evaluate anti-proliferative and apoptosis-inducing effect of TB on NSCLC (A549) cells, using MTT assay, morphological observation (DAPI staining), in situ terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and annexin-V/PI flow cytometry. Subsequently, the expression of several genes associated with cell proliferation and apoptosis were detected by real time PCR assay to explore its potential underlying mechanism. TB was revealed to inhibit cell proliferation of A549 cells in a concentration-dependent and time-dependent manner. Morphological observation, TUNEL assay and flow cytometric analysis evidenced an apoptosis-inducing effect of TB on A549 cells in a concentration-dependent manner. The real time PCR assay demonstrated that TB down-regulated the expression of TOPO I, TOPO II, and BCL-2, and up-regulated the expression of E2F1, P53, GADD45, BAX, BIM, and CASP 3,7,8,9, which suggests an activation of P53-mediated apoptotic (caspase-dependent) pathway in response to TB treatment. The western blot analysis showed a similar trend for the corresponding protein expression (P53, Bax, Bcl-2, caspase 3,9, and PARP) and further revealed DNA damage as a trigger of the apoptosis (phosphorylation of histone H2A.X). Accordingly, TB can be speculated as a DNA damage inducer and topoisomerase (Topo I and Topo II) inhibitor that can up-regulate P53 expression and subsequently modulate the expression of the downstream genes to induce cell proliferation inhibition and apoptosis of A549 cells. Our results indicate that TB exhibits its anti-NSCLC activity via a P53-dependent mechanism, which may be a promising candidate of natural product for anti-cancer drug development in the treatment of NSCLC.

Addresses

Institute for Cell-Based Drug Development of Zhejiang Province, S-Evans Biosciences, Ltd. Hangzhou, China.

Autoren

Feifei Wu
Li Zhou
Wangdong Jin
Weiji Yang
Ying Wang
Bo Yan
Wenlin Du
Qiang Zhang
Lei Zhang
Yonghua Guo
Jin Zhang
Letian Shan
Thomas Efferth
Thomas Efferth

DOI

10.3389/fphar.2016.00465

eISSN

1663-9812

Externe Identifier

PubMed Identifier: 27994550
PubMed Central ID: PMC5133245

Funding acknowledgements

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

2016

Open access status

Open Access

Paginierung

465

Datum der Veröffentlichung

2016

Status

Published

Publisher licence

CC BY

Datum der Datenerfassung

2016

Titel

Anti-Proliferative and Apoptosis-Inducing Effect of Theabrownin against Non-small Cell Lung Adenocarcinoma A549 Cells.

Sub types

research-article
Journal Article

Ausgabe der Zeitschrift

Files

https://www.frontiersin.org/articles/10.3389/fphar.2016.00465/pdf https://europepmc.org/articles/PMC5133245?pdf=render

Data source: Europe PubMed Central

Abstract

With the highest cancer incidence rate, lung cancer, especially non-small cell lung cancer (NSCLC), is the leading cause of cancer death in the world. Tea (leaves of Camellia sinensis) has been widely used as a traditional beverage beneficial to human health, including anti-NSCLC activity. Theabrownin (TB) is one major kind of tea pigment responsible for the beneficial effects of tea liquor. However, its effect on NSCLC is unknown. The aim of the present study was to evaluate anti-proliferative and apoptosis-inducing effect of TB on NSCLC (A549) cells, using MTT assay, morphological observation (DAPI staining), in situ terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and annexin-V/PI flow cytometry. Subsequently, the expression of several genes associated with cell proliferation and apoptosis were detected by real time PCR assay to explore its potential underlying mechanism. TB was revealed to inhibit cell proliferation of A549 cells in a concentration-dependent and time-dependent manner. Morphological observation, TUNEL assay and flow cytometric analysis evidenced an apoptosis-inducing effect of TB on A549 cells in a concentration-dependent manner. The real time PCR assay demonstrated that TB down-regulated the expression of TOPO I, TOPO II, and BCL-2, and up-regulated the expression of E2F1, P53, GADD45, BAX, BIM, and CASP 3,7,8,9, which suggests an activation of P53-mediated apoptotic (caspase-dependent) pathway in response to TB treatment. The western blot analysis showed a similar trend for the corresponding protein expression (P53, Bax, Bcl-2, caspase 3,9, and PARP) and further revealed DNA damage as a trigger of the apoptosis (phosphorylation of histone H2A.X). Accordingly, TB can be speculated as a DNA damage inducer and topoisomerase (Topo I and Topo II) inhibitor that can up-regulate P53 expression and subsequently modulate the expression of the downstream genes to induce cell proliferation inhibition and apoptosis of A549 cells. Our results indicate that TB exhibits its anti-NSCLC activity via a P53-dependent mechanism, which may be a promising candidate of natural product for anti-cancer drug development in the treatment of NSCLC.

Date of acceptance

2016

Autoren

Feifei Wu
Li Zhou
Wangdong Jin
Weiji Yang
Ying Wang
Bo Yan
Wenlin Du
Qiang Zhang
Lei Zhang
Yonghua Guo
Jin Zhang
Letian Shan
Thomas Efferth

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/27994550

DOI

10.3389/fphar.2016.00465

Externe Identifier

PubMed Central ID: PMC5133245

ISSN

1663-9812

Zeitschrift

Front Pharmacol

Schlüsselwörter

A549 cells
P53
apoptosis
lung cancer
theabrownin

Sprache

eng

Country

Switzerland

Paginierung

465

Datum der Veröffentlichung

2016

Status

Published online

Titel

Anti-Proliferative and Apoptosis-Inducing Effect of Theabrownin against Non-small Cell Lung Adenocarcinoma A549 Cells.

Sub types

Journal Article

Ausgabe der Zeitschrift

Data source: PubMed

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Pharmazeutische Biologie

Anti-Proliferative and Apoptosis-Inducing Effect of Theabrownin against Non-small Cell Lung Adenocarcinoma A549 Cells

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