Molecules 2013, 18(9), 10242-10253; doi:10.3390/molecules180910242
Article

Brefeldin A Effectively Inhibits Cancer Stem Cell-Like Properties and MMP-9 Activity in Human Colorectal Cancer Colo 205 Cells

1,†email, 2,†email, 3email, 1email, 2email, 4,* email and 5,* email
Received: 30 May 2013; in revised form: 14 August 2013 / Accepted: 19 August 2013 / Published: 22 August 2013
(This article belongs to the Section Metabolites)
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.
Abstract: Cancer stem cells (CSCs) are a small subset of cancer cells with indefinite potential for self-renewal and the capacity to drive tumorigenesis. Brefeldin A (BFA) is an antibiotic that is known to block protein transport and induce endoplasmic reticulum (ER) stress in eukaryotic cells, but its effects on colorectal CSCs are unknown. We investigated the inhibitory effect of BFA on human colorectal cancer Colo 205 cells. We found that BFA effectively reduced the survival of suspension Colo 205 cells (IC50 = ~15 ng/mL) by inducing apoptosis, and inhibited the clonogenic activity of Colo 205 CSCs in tumorsphere formation assay and soft agar colony formation assay in the same nanogram per milliliter range. We also discovered that at such low concentrations, BFA effectively induced endoplasmic reticulum (ER) stress response as indicated by the increased mRNA expression of ER stress-related genes, such as glucose-regulated protein 78 (GRP78), X-box binding protein 1 (XBP1), and C/EBP homologous protein (CHOP). Finally, we found that BFA reduced the activity of matrix metallopeptidase 9 (MMP-9). These findings suggest that BFA can effectively suppress the progression of colorectal cancer during the tumorigenesis and metastasis stages. These results may lead to the development of novel therapies for the treatment of colorectal cancer.
Keywords: brefeldin A; cancer stem cell; colorectal cancer; matrix metallopeptidase; clonogenesis
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MDPI and ACS Style

Tseng, C.-N.; Huang, C.-F.; Cho, C.-L.; Chang, H.-W.; Huang, C.-W.; Chiu, C.-C.; Chang, Y.-F. Brefeldin A Effectively Inhibits Cancer Stem Cell-Like Properties and MMP-9 Activity in Human Colorectal Cancer Colo 205 Cells. Molecules 2013, 18, 10242-10253.

AMA Style

Tseng C-N, Huang C-F, Cho C-L, Chang H-W, Huang C-W, Chiu C-C, Chang Y-F. Brefeldin A Effectively Inhibits Cancer Stem Cell-Like Properties and MMP-9 Activity in Human Colorectal Cancer Colo 205 Cells. Molecules. 2013; 18(9):10242-10253.

Chicago/Turabian Style

Tseng, Chao-Neng; Huang, Chien-Fu; Cho, Chung-Lung; Chang, Hsueh-Wei; Huang, Chao-Wei; Chiu, Chien-Chih; Chang, Yung-Fu. 2013. "Brefeldin A Effectively Inhibits Cancer Stem Cell-Like Properties and MMP-9 Activity in Human Colorectal Cancer Colo 205 Cells." Molecules 18, no. 9: 10242-10253.


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