Brefeldin A reduces anchorage-independent survival, cancer stem cell potential and migration of MDA-MB-231 human breast cancer cells

  • Molecules. 2014 Oct 29;19(11):17464-77. doi: 10.3390/molecules191117464.
Chao-Neng Tseng  1 ,  Yi-Ren Hong  2 ,  Hsueh-Wei Chang  3 ,  Tsai-Jung Yu  4 ,  Ting-Wei Hung  5 ,  Ming-Feng Hou  6 ,  Shyng-Shiou F Yuan  7 ,  Chung-Lung Cho  8 ,  Chien-Tsung Liu  9 ,  Chien-Chih Chiu  10 ,  Chih-Jen Huang  11
Affiliations
  • 1. Department of Biomedical Science and Environmental Biology, Translational Research Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. [email protected].
  • 2. Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 80424, Taiwan. [email protected].
  • 3. Department of Biomedical Science and Environmental Biology, Translational Research Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. [email protected].
  • 4. Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. [email protected].
  • 5. Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. [email protected].
  • 6. Cancer Center and Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan. [email protected].
  • 7. Translational Research Center, Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan. [email protected].
  • 8. Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 80424, Taiwan. [email protected].
  • 9. Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. [email protected].
  • 10. Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. [email protected].
  • 11. Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. [email protected].
PMID: 25356567 DOI: 10.3390/molecules191117464
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.

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