Development of resistance towards artesunate in mda-mb-231 human breast cancer cells

Autoren

Beatrice Bachmeier
Iduna Fichtner
Peter H Killian
Emanuel Kronski
Ulrich Pfeffer
Thomas Efferth

Autoren-URL

https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000291052200078&DestLinkType=FullRecord&DestApp=WOS_CPL

DOI

10.1371/journal.pone.0020550

Externe Identifier

Clarivate Analytics Document Solution ID: 769XS
PubMed Identifier: 21637790

ISSN

1932-6203

Ausgabe der Veröffentlichung

5

Zeitschrift

PLOS ONE

Artikelnummer

ARTN e20550

Datum der Veröffentlichung

2011

Status

Published

Titel

Development of Resistance towards Artesunate in MDA-MB-231 Human Breast Cancer Cells

Sub types

Article

Ausgabe der Zeitschrift

6

Data source: Web of Science (Lite)

Autoren

Beatrice Bachmeier
Iduna Fichtner
Peter H Killian
Emanuel Kronski
Ulrich Pfeffer
Thomas Efferth

DOI

10.1371/journal.pone.0020550

Editoren

Andrei L Gartel

eISSN

1932-6203

Ausgabe der Veröffentlichung

5

Zeitschrift

PLoS ONE

Sprache

en

Online publication date

2011

Paginierung

e20550 - e20550

Status

Published online

Herausgeber

Public Library of Science (PLoS)

Herausgeber URL

http://dx.doi.org/10.1371/journal.pone.0020550

Datum der Datenerfassung

2023

Titel

Development of Resistance towards Artesunate in MDA-MB-231 Human Breast Cancer Cells

Ausgabe der Zeitschrift

6

Data source: Crossref

Abstract

Breast cancer is the most common cancer and the second leading cause of cancer death in industrialized countries. Systemic treatment of breast cancer is effective at the beginning of therapy. However, after a variable period of time, progression occurs due to therapy resistance. Artesunate, clinically used as anti-malarial agent, has recently revealed remarkable anti-tumor activity offering a role as novel candidate for cancer chemotherapy. We analyzed the anti-tumor effects of artesunate in metastasizing breast carcinoma in vitro and in vivo. Unlike as expected, artesunate induced resistance in highly metastatic human breast cancer cells MDA-MB-231. Likewise acquired resistance led to abolishment of apoptosis and cytotoxicity in pre-treated MDA-MB-231 cells. In contrast, artesunate was more cytotoxic towards the less tumorigenic MDA-MB-468 cells without showing resistance. Unraveling the underlying molecular mechanisms, we found that resistance was induced due to activation of the tumor progression related transcription factors NFκB and AP-1. Thereby transcription, expression and activity of the matrix-degrading enzyme MMP-1, whose function is correlated with increased invasion and metastasis, was up-regulated upon acquisition of resistance. Additionally, activation of the apoptosis-related factor NFκB lead to increased expression of ant-apoptotic bcl2 and reduced expression of pro-apoptotic bax. Application of artesunate in vivo in a model of xenografted breast cancer showed, that tumors growth was not efficiently abolished as compared to the control drug doxorubicin. Taken together our in vitro and in vivo results correlate well showing for the first time that artesunate induces resistance in highly metastatic breast tumors.

Addresses

Department of Clinical Chemistry and Clinical Biochemistry, Ludwig-Maximilians-University, Munich, Germany.

Autoren

Beatrice Bachmeier
Iduna Fichtner
Peter H Killian
Emanuel Kronski
Ulrich Pfeffer
Thomas Efferth
Thomas Efferth

DOI

10.1371/journal.pone.0020550

eISSN

1932-6203

Externe Identifier

PubMed Identifier: 21637790
PubMed Central ID: PMC3102747

Open access

true

ISSN

1932-6203

Ausgabe der Veröffentlichung

5

Zeitschrift

PloS one

Schlüsselwörter

Cell Line, Tumor
Animals
Humans
Mice
Mice, Nude
Breast Neoplasms
Artemisinins
NF-kappa B
Transcription Factor AP-1
Electrophoretic Mobility Shift Assay
Xenograft Model Antitumor Assays
Apoptosis
Cell Survival
Drug Resistance, Neoplasm
Female
bcl-2-Associated X Protein
Matrix Metalloproteinase 1
Artesunate

Sprache

eng

Medium

Print-Electronic

Online publication date

2011

Open access status

Open Access

Paginierung

e20550

Datum der Veröffentlichung

2011

Status

Published

Publisher licence

CC BY

Datum der Datenerfassung

2011

Titel

Development of resistance towards artesunate in MDA-MB-231 human breast cancer cells.

Sub types

research-article
Journal Article

Ausgabe der Zeitschrift

6

Files

https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0020550&type=printable https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21637790/pdf/?tool=EBI https://europepmc.org/articles/PMC3102747?pdf=render

Data source: Europe PubMed Central

Abstract

Breast cancer is the most common cancer and the second leading cause of cancer death in industrialized countries. Systemic treatment of breast cancer is effective at the beginning of therapy. However, after a variable period of time, progression occurs due to therapy resistance. Artesunate, clinically used as anti-malarial agent, has recently revealed remarkable anti-tumor activity offering a role as novel candidate for cancer chemotherapy. We analyzed the anti-tumor effects of artesunate in metastasizing breast carcinoma in vitro and in vivo. Unlike as expected, artesunate induced resistance in highly metastatic human breast cancer cells MDA-MB-231. Likewise acquired resistance led to abolishment of apoptosis and cytotoxicity in pre-treated MDA-MB-231 cells. In contrast, artesunate was more cytotoxic towards the less tumorigenic MDA-MB-468 cells without showing resistance. Unraveling the underlying molecular mechanisms, we found that resistance was induced due to activation of the tumor progression related transcription factors NFκB and AP-1. Thereby transcription, expression and activity of the matrix-degrading enzyme MMP-1, whose function is correlated with increased invasion and metastasis, was up-regulated upon acquisition of resistance. Additionally, activation of the apoptosis-related factor NFκB lead to increased expression of ant-apoptotic bcl2 and reduced expression of pro-apoptotic bax. Application of artesunate in vivo in a model of xenografted breast cancer showed, that tumors growth was not efficiently abolished as compared to the control drug doxorubicin. Taken together our in vitro and in vivo results correlate well showing for the first time that artesunate induces resistance in highly metastatic breast tumors.

Date of acceptance

2011

Autoren

Beatrice Bachmeier
Iduna Fichtner
Peter H Killian
Emanuel Kronski
Ulrich Pfeffer
Thomas Efferth

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/21637790

DOI

10.1371/journal.pone.0020550

eISSN

1932-6203

Externe Identifier

PubMed Central ID: PMC3102747

Ausgabe der Veröffentlichung

5

Zeitschrift

PLoS One

Schlüsselwörter

Animals
Apoptosis
Artemisinins
Artesunate
Breast Neoplasms
Cell Line, Tumor
Cell Survival
Drug Resistance, Neoplasm
Electrophoretic Mobility Shift Assay
Female
Humans
Matrix Metalloproteinase 1
Mice
Mice, Nude
NF-kappa B
Transcription Factor AP-1
Xenograft Model Antitumor Assays
bcl-2-Associated X Protein

Sprache

eng

Country

United States

Paginierung

e20550

PII

PONE-D-10-01503

Datum der Veröffentlichung

2011

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2011

Titel

Development of resistance towards artesunate in MDA-MB-231 human breast cancer cells.

Sub types

Journal Article

Ausgabe der Zeitschrift

6

Data source: PubMed

Development of resistance towards artesunate in mda-mb-231 human breast cancer cells

Files

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