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.
Highlights
Mounting evidence indicates that most types of cancer, including breast cancer, originate from a small subset of cancer stem cells (CSCs) [1,2,3,4]
We tested the effect of Brefeldin A (BFA) on the clonogenic potential of MDA-MB-231 by pretreating adherent MDA-MB-231 cells with 0–50 μg/mL BFA for 24 h and allowing colonies to be generated from 1000 viable cells per well in a 6-well plate for 12 d
To explore the underlining mechanism responsible for the effects of BFA, we examined the expression of selected proteins involved in endoplasmic reticulum (ER) stress response, apoptosis regulation, epithelial-mesenchymal transition, and maintenance of cancer stem cell properties by western blotting (Figure 4)
Summary
Mounting evidence indicates that most types of cancer, including breast cancer, originate from a small subset of cancer stem cells (CSCs) [1,2,3,4]. These CSCs are able to self-renew and give rise to other cancer cells that form a tumor mass [5,6]. We investigated the effects of BFA on the CSC properties of MDA-MB-231 human breast cancer cells and the potential underlying mechanism
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
