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

Molecules

Chao-Neng Tseng³  Yi-Ren Hong⁶  Hsueh-Wei Chang³  Tsai-Jung Yu⁵  Ting-Wei Hung⁵  Ming-Feng Hou²  Shyng-Shiou F. Yuan⁷  Chung-Lung Cho⁶  Chien-Tsung Liu⁴  Chien-Chih Chiu⁴  Chih-Jen Huang¹ 

[1] Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan;Cancer Center and Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan; E-Mail:;Department of Biomedical Science and Environmental Biology, Translational Research Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; E-Mails:;Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; E-Mails:;Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; E-Mails:;Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 80424, Taiwan; E-Mail:;Translational Research Center, Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan; E-Mail:

关键词: brefeldin A;    cancer stem cell;    ER stress;    breast cancer;   

DOI  :  10.3390/molecules191117464

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.