Development of resistance towards artesunate in MDA-MB-231 human breast cancer cells
Language: 
English
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 NF?B 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 NF?B 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.

Author(s): 
Bachmeier, Beatrice
Fichtner, Iduna
Killian, Peter H.
Kronski, Emanuel
Pfeffer, Ulrich
Efferth, Thomas
Item Type: 
Journal Article
Publication Title: 
PloS One
Journal Abbreviation: 
PLoS ONE
Publication Date: 
2011
Publication Year: 
2011
Pages: 
e20550
Volume: 
6
Issue: 
5
ISSN: 
1932-6203
DOI: 
10.1371/journal.pone.0020550
Library Catalog: 
PubMed
Extra: 
PMID: 21637790 PMCID: PMC3102747

Turabian/Chicago Citation

Beatrice Bachmeier, Iduna Fichtner, Peter H. Killian, Emanuel Kronski, Ulrich Pfeffer and Thomas Efferth. 2011. "Development of resistance towards artesunate in MDA-MB-231 human breast cancer cells." PloS One 6: 5: e20550. 10.1371/journal.pone.0020550.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1371/journal.pone.0020550 | issn = 1932-6203 | volume = 6 | pages = e20550 | last = Bachmeier | first = Beatrice | coauthors = Fichtner, Iduna, Killian, Peter H., Kronski, Emanuel, Pfeffer, Ulrich, Efferth, Thomas | title = Development of resistance towards artesunate in MDA-MB-231 human breast cancer cells | journal = PloS One | date = 2011 | pmid = | pmc = }} </ref>