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Molecules 2014, 19(11), 17464-17477; doi:10.3390/molecules191117464

Brefeldin A Reduces Anchorage-Independent Survival, Cancer Stem Cell Potential and Migration of MDA-MB-231 Human Breast Cancer Cells

1
Department of Biomedical Science and Environmental Biology, Translational Research Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
2
Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
3
Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
4
Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
5
Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
6
Cancer Center and Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan
7
Translational Research Center, Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan
8
Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
9
Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
10
Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
These authors contributed equally to this study.
*
Author to whom correspondence should be addressed.
Received: 8 July 2014 / Revised: 27 October 2014 / Accepted: 27 October 2014 / Published: 29 October 2014
(This article belongs to the Section Natural Products)
View Full-Text   |   Download PDF [8672 KB, uploaded 29 October 2014]   |  

Abstract

Cancer stem cells (CSCs) are a subset of cancer cells in tumors or established cancer cell lines that can initiate and sustain the growth of tumors in vivo. Cancer stem cells can be enriched in serum-free, suspended cultures that allow the formation of tumorspheres over several days to weeks. Brefeldin A (BFA) is a mycotoxin that induces endoplasmic reticulum (ER) stress in eukaryotic cells. We found that BFA, at sub-microgram per milliliter concentrations, preferentially induced cell death in MDA-MB-231 suspension cultures (EC50: 0.016 µg/mL) compared to adhesion cultures. BFA also effectively inhibited clonogenic activity and the migration and matrix metalloproteinases-9 (MMP-9) activity of MDA-MB-231 cells. Western blotting analysis indicated that the effects of BFA may be mediated by the down-regulation of breast CSC marker CD44 and anti-apoptotic proteins Bcl-2 and Mcl-1, as well as the reversal of epithelial-mesenchymal transition. Furthermore, BFA also displayed selective cytotoxicity toward suspended MDA-MB-468 cells, and suppressed tumorsphere formation in T47D and MDA-MB-453 cells, suggesting that BFA may be effective against breast cancer cells of various phenotypes. View Full-Text
Keywords: brefeldin A; cancer stem cell; ER stress; breast cancer brefeldin A; cancer stem cell; ER stress; breast cancer
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Tseng, C.-N.; Hong, Y.-R.; Chang, H.-W.; Yu, T.-J.; Hung, T.-W.; Hou, M.-F.; Yuan, S.-S.F.; Cho, C.-L.; Liu, C.-T.; Chiu, C.-C.; Huang, C.-J. Brefeldin A Reduces Anchorage-Independent Survival, Cancer Stem Cell Potential and Migration of MDA-MB-231 Human Breast Cancer Cells. Molecules 2014, 19, 17464-17477.

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