Brefeldin A Reduces Anchorage-Independent Survival, Cancer Stem Cell Potential and Migration of MDA-MB-231 Human Breast Cancer Cells
Chao-Neng Tseng,
Yi-Ren Hong,
Hsueh-Wei Chang,
Tsai-Jung Yu,
Ting-Wei Hung,
Ming-Feng Hou,
Shyng-Shiou F. Yuan,
Chung-Lung Cho,
Chien-Tsung Liu,
Chien-Chih Chiu,
Chih-Jen Huang
Affiliations
Chao-Neng Tseng
Department of Biomedical Science and Environmental Biology, Translational Research Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
Yi-Ren Hong
Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
Hsueh-Wei Chang
Department of Biomedical Science and Environmental Biology, Translational Research Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
Tsai-Jung Yu
Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
Ting-Wei Hung
Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
Ming-Feng Hou
Cancer Center and Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan
Shyng-Shiou F. Yuan
Translational Research Center, Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan
Chung-Lung Cho
Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
Chien-Tsung Liu
Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
Chien-Chih Chiu
Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
Chih-Jen Huang
Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
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.
