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

Publication type:
Conference
Metadata:
Autoren
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000209701300003&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1158/1538-7445.AM2011-709
eISSN
1538-7445
Externe Identifier
  • Clarivate Analytics Document Solution ID: V43SO
ISSN
0008-5472
Zeitschrift
CANCER RESEARCH
Datum der Veröffentlichung
2011
Status
Published
Titel
Development of resistance towards artesunate in MDA-MB-231 human breast cancer cells
Ausgabe der Zeitschrift
71

Data source: Web of Science (Lite)

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Abstract
<jats:title>Abstract</jats:title> <jats:p>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 (ART), 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 ART in metastasizing breast carcinoma in vitro and in vivo. Unlike as expected, ART 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, ART 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 ART 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 ART induces resistance in highly metastatic breast tumors.</jats:p> <jats:p>Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 709. doi:10.1158/1538-7445.AM2011-709</jats:p>
Autoren
DOI
10.1158/1538-7445.am2011-709
eISSN
1538-7445
ISSN
0008-5472
Ausgabe der Veröffentlichung
8_Supplement
Zeitschrift
Cancer Research
Paginierung
709 - 709
Datum der Veröffentlichung
2011
Status
Published
Herausgeber
American Association for Cancer Research (AACR)
Herausgeber URL
http://dx.doi.org/10.1158/1538-7445.am2011-709
Datum der Datenerfassung
2022
Titel
Abstract 709: Development of resistance towards artesunate in MDA-MB-231 human breast cancer cells
Ausgabe der Zeitschrift
71

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