title: Brefeldin a effectively inhibits cancer stem cell-like properties and MMP-9 activity in human colorectal cancer Colo 205 cells.
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.
authors: Graduate Institute of Natural Products, Department of Biomedical Science and Environmental Biology, Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
authors: Chao-Neng
authors: CN
authors: Tseng
authors: Chien-Fu
authors: CF
authors: Huang
authors: Chung-Lung
authors: CL
authors: Cho
authors: Hsueh-Wei
authors: HW
authors: Chang
authors: Chao-Wei
authors: CW
authors: Huang
authors: Chien-Chih
authors: CC
authors: Chiu
authors: Yung-Fu
authors: YF
authors: Chang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D020126:Brefeldin A / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms; D004354:Drug Screening Assays, Antitumor; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000201:enzymology; D018874:Spheroids, Cellular / Q000187:drug effects / Q000201:enzymology
chemical_list: D000970:Antineoplastic Agents; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D020126:Brefeldin A; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
references: Cancers (Basel). 2011 Jan 1;3(1):319-39
references: 21318087
references: Cell Res. 2007 Jan;17(1):3-14
references: 17179981
references: Molecules. 2012 Dec 27;18(1):354-72
references: 23271470
references: Neurobiol Dis. 2007 Feb;25(2):217-29
references: 17141509
references: J Clin Invest. 2013 May;123(5):1911-8
references: 23635789
references: Methods. 2001 Dec;25(4):402-8
references: 11846609
references: J Antibiot (Tokyo). 1968 Feb;21(2):160-1
references: 4299889
references: Cell. 1999 Apr 16;97(2):153-5
references: 10219235
references: FASEB J. 2005 Feb;19(2):234-6
references: 15550552
references: PLoS One. 2012;7(2):e31864
references: 22359637
references: Cell Biol Int. 2013 Jun;37(6):521-32
references: 23494837
references: Cancers (Basel). 2011 Mar 22;3(1):1467-79
references: 24212669
references: J Biomed Sci. 2010 Jan 26;17:5
references: 20102617
references: Methods Cell Biol. 2011;103:55-98
references: 21722800
references: Nat Immunol. 2003 Apr;4(4):321-9
references: 12612580
references: Toxicology. 2009 Apr 28;258(2-3):164-75
references: 19428936
references: Cell Stress Chaperones. 2012 Mar;17(2):275-9
references: 22038282
references: Cell. 2009 Aug 21;138(4):645-659
references: 19682730
references: Cancer Metastasis Rev. 2006 Mar;25(1):9-34
references: 16680569
references: BMC Complement Altern Med. 2012 Aug 31;12:142
references: 22937998
references: PLoS One. 2007 Sep 12;2(9):e835
references: 17848986
references: Pharmacoeconomics. 2013 Jul;31(7):577-88
references: 23636661
references: CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90
references: 21296855
references: Evid Based Complement Alternat Med. 2013;2013:702869
references: 23533514
references: Curr Top Med Chem. 2011;11(13):1592-8
references: 21446911
references: Mol Cell Biol. 2005 Jun;25(11):4529-40
references: 15899857
references: Molecules. 2012 Jul 03;17(7):8010-21
references: 22759914
references: FEBS Lett. 2012 Sep 21;586(19):3111-6
references: 22884571
references: Nature. 2001 Nov 1;414(6859):105-11
references: 11689955
references: Oncogene. 2013 Jan 31;32(5):544-53
references: 22469978
references: Tumour Biol. 2013 Aug;34(4):2041-51
references: 23681802
references: Nat Methods. 2012 Jul;9(7):671-5
references: 22930834
references: Biochem Biophys Res Commun. 2011 Dec 16;416(3-4):246-51
references: 22074823
references: Molecules. 2012 Dec 21;18(1):128-39
references: 23344192
references: Molecules. 2013 Feb 26;18(3):2539-48
references: 23442930
references: J Agric Food Chem. 2011 Apr 27;59(8):4288-93
references: 21391609