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

Molecules

Chao-Neng Tseng¹  Chien-Fu Huang³  Chung-Lung Cho⁴  Hsueh-Wei Chang¹  Chao-Wei Huang³  Chien-Chih Chiu² 

[1] Graduate Institute of Natural Products, Department of Biomedical Science and Environmental Biology, Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan; E-Mails:;Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan;Department of Biological Sciences and Technology, I-Shou University, Kaohsiung 824, Taiwan; E-Mails:;Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan; E-Mail:

关键词: brefeldin A;    cancer stem cell;    colorectal cancer;    matrix metallopeptidase;    clonogenesis;   

DOI  :  10.3390/molecules180910242

来源: mdpi

【 摘 要 】

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.

【 授权许可】

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