Cytotoxicity of 5-fluorouracil: Effect on endothelial differentiation via cell cycle inhibition in mouse embryonic stem cells
- Authors
- Kim, Gi Dae; Rhee, Gyu-Seek; Chung, Hyung-Min; Chee, Kew-Mahn; Kim, Gi Jin
- Issue Date
- 6월-2009
- Publisher
- PERGAMON-ELSEVIER SCIENCE LTD
- Keywords
- Mouse embryonic stem cells; Viability; Proliferation; Differentiation; 5-Fluorouracil; Cytotoxicity; cDNA microarray; Cell cycle
- Citation
- TOXICOLOGY IN VITRO, v.23, no.4, pp.719 - 727
- Indexed
- SCIE
SCOPUS
- Journal Title
- TOXICOLOGY IN VITRO
- Volume
- 23
- Number
- 4
- Start Page
- 719
- End Page
- 727
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/119983
- DOI
- 10.1016/j.tiv.2009.02.012
- ISSN
- 0887-2333
- Abstract
- Embryonic stem cells (ESCs) are known to characteristics for pluripotency and self-renewal, but the precise mechanisms of ES-derived cells to specific toxicants have not been determined. Here, we evaluated the cytotoxicity of 5-fluorouracil (5-FU) and see its effect on cell viability, proliferation, and differentiation in mouse ESC-derived endothelial differentiation. Mouse ESCs were exposed to 5-FU (10 mu M) and combined with probucol (50 mu M) for 24 h, which is an antagonist of 5-FU. Changes in gene expression as a result of 5-FU exposure in mouse ESC-derived endothelial precursor cells (ES-EPCs) were assessed using an oligonucleotide microarray (AB1700). The expression of Oct-4 was decreased during the differentiation of mouse ESCs into endothelial cells; otherwise, the expression of PECAM was increased. Mouse ES-EPCs were shown to have a decrease in viability (49.8%) and PECAM expression, and induce G1/S phase (31.1%/60.6%) when compared with/without treatment of 5-FU. Expression of cell cycle-related proteins was increased in enclothelial precursor cells exposed to 5-FU without probucol treatment. From theses results suggest that 5-FU inhibit enclothelial differentiation as well as inducing the G1/S phase arrest. We propose that mouse ES-ElPCs might be a useful too[ for screening the cytotoxicity of compounds in enclothelial cells. (C) 2009 Elsevier Ltd. All rights reserved.
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