产品号 #73012_C
Protein trafficking inhibitor; Inhibits Sec7-containing guanine-exchange factor (GEF)
概述
Brefeldin A is a fungal lactone antibiotic, produced by many species, including Eupenicillium brefeldianum (Klausner et al.). It reversibly interferes with protein trafficking and secretion mediated by the Golgi apparatus and endoplasmic reticulum by indirect inhibition of ADP-ribosylation factor (ARF; Klausner et al.; Helms & Rothman; Robinson et al.; Morinaga et al.; Moss & Vaughan; Nebenführ et al.; Ktistakis et al.). Brefeldin A binds to Sec7-containing guanine-exchange factor (GEF) at the ARF-GDP-Sec7 interface, preventing the conformational change required to release GDP and activate ARF (Mossessova et al.).
CELL LINE DEVELOPMENT
· Improves clustered regularly interspaced palindromic repeats (CRISPR)-mediated homology-directed repair (HDR) in mouse embryonic stem cells (Yu et al.).
CANCER RESEARCH
· Induces apoptosis in human leukemia (HL60, K562) and colon carcinoma (HT-29) cell lines (Shao et al.).
· Reduces survival, induces apoptosis and inhibits clonogenic activity of Colo 205 colorectal cancer stem cell line (Tseng et al.).
Cell Type
Cancer Cells and Cell Lines, Pluripotent Stem Cells
Species
Human, Mouse, Non-Human Primate, Other, Rat
Application
Antibiotic
Area of Interest
Cancer, Cell Line Development, Stem Cell Biology
CAS Number
20350-15-6
Chemical Formula
C₁₆H₂₄O₄
Purity
≥ 98%
Target
GEF
Protocols and Documentation
Find supporting information and directions for use in the Product Information Sheet or explore additional protocols below.
Resources and Publications
Educational Materials (2)
Publications (11)
Small molecules enhance CRISPR genome editing in pluripotent stem cells. Cell stem cell 2015 FEB
Abstract
The bacterial CRISPR-Cas9 system has emerged as an effective tool for sequence-specific gene knockout through non-homologous end joining (NHEJ), but it remains inefficient for precise editing of genome sequences. Here we develop a reporter-based screening approach for high-throughput identification of chemical compounds that can modulate precise genome editing through homology-directed repair (HDR). Using our screening method, we have identified small molecules that can enhance CRISPR-mediated HDR efficiency, 3-fold for large fragment insertions and 9-fold for point mutations. Interestingly, we have also observed that a small molecule that inhibits HDR can enhance frame shift insertion and deletion (indel) mutations mediated by NHEJ. The identified small molecules function robustly in diverse cell types with minimal toxicity. The use of small molecules provides a simple and effective strategy to enhance precise genome engineering applications and facilitates the study of DNA repair mechanisms in mammalian cells.
Brefeldin a effectively inhibits cancer stem cell-like properties and MMP-9 activity in human colorectal cancer Colo 205 cells. Molecules (Basel, Switzerland) 2013
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.
The endosomal system of plants: charting new and familiar territories. Plant physiology 2008 AUG
Abstract
PRODUCTS ARE FOR RESEARCH USE ONLY AND NOT INTENDED FOR HUMAN OR ANIMAL DIAGNOSTIC OR THERAPEUTIC USES UNLESS OTHERWISE STATED. FOR ADDITIONAL INFORMATION ON QUALITY AT STEMCELL, REFER TO WWW.STEMCELL.COM/COMPLIANCE.
