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

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, clinical...

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Autores principales:	Beatrice Bachmeier, Iduna Fichtner, Peter H Killian, Emanuel Kronski, Ulrich Pfeffer, Thomas Efferth
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f2440a68bebd4698b08b8cc0c323a8d9
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spelling	oai:doaj.org-article:f2440a68bebd4698b08b8cc0c323a8d92021-11-18T06:53:11ZDevelopment of resistance towards artesunate in MDA-MB-231 human breast cancer cells.1932-620310.1371/journal.pone.0020550https://doaj.org/article/f2440a68bebd4698b08b8cc0c323a8d92011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21637790/?tool=EBIhttps://doaj.org/toc/1932-6203Breast 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.Beatrice BachmeierIduna FichtnerPeter H KillianEmanuel KronskiUlrich PfefferThomas EfferthPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 5, p e20550 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Beatrice Bachmeier Iduna Fichtner Peter H Killian Emanuel Kronski Ulrich Pfeffer Thomas Efferth Development of resistance towards artesunate in MDA-MB-231 human breast cancer cells.
description	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.
format	article
author	Beatrice Bachmeier Iduna Fichtner Peter H Killian Emanuel Kronski Ulrich Pfeffer Thomas Efferth
author_facet	Beatrice Bachmeier Iduna Fichtner Peter H Killian Emanuel Kronski Ulrich Pfeffer Thomas Efferth
author_sort	Beatrice Bachmeier
title	Development of resistance towards artesunate in MDA-MB-231 human breast cancer cells.
title_short	Development of resistance towards artesunate in MDA-MB-231 human breast cancer cells.
title_full	Development of resistance towards artesunate in MDA-MB-231 human breast cancer cells.
title_fullStr	Development of resistance towards artesunate in MDA-MB-231 human breast cancer cells.
title_full_unstemmed	Development of resistance towards artesunate in MDA-MB-231 human breast cancer cells.
title_sort	development of resistance towards artesunate in mda-mb-231 human breast cancer cells.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/f2440a68bebd4698b08b8cc0c323a8d9
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Development of resistance towards artesunate in MDA-MB-231 human breast cancer cells.

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