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A New 2-Pyrone Derivative, 5-Bromo-3-(3-hydroxyprop-1-ynyl)-2H-pyran-2-one, Suppresses Stemness in Glioma Stem-Like Cells

Title
A New 2-Pyrone Derivative, 5-Bromo-3-(3-hydroxyprop-1-ynyl)-2H-pyran-2-one, Suppresses Stemness in Glioma Stem-Like Cells
Author
오영석
Keywords
GROWTH; IDENTIFICATION
Issue Date
2012-09
Publisher
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
Citation
MOLECULAR PHARMACOLOGY, 82, 3, 400-407
Abstract
Glioma cells with stem cell properties, termed glioma stem-like cells (GSCs), have been linked to tumor formation, maintenance, and progression and are responsible for the failure of chemotherapy and radiotherapy. Because conventional glioma treatments often fail to eliminate GSCs completely, residual surviving GSCs are able to repopulate the tumor. Compounds that target GSCs might be helpful in overcoming resistance to anticancer treatments in human brain tumors. In this study, we showed that 5-bromo-3-(3-hydroxyprop-1-ynyl)-2H-pyran-2-one (BHP), a new 2-pyrone derivative, suppressed the maintenance of the GSC population in both a glioma cell line and patient-derived glioma cells. Treatment of GSCs with BHP effectively inhibited sphere formation and suppressed the CD133(+) cell population. Treatment with BHP also suppressed expression of the stemness-regulating transcription factors Sox2, Notch2, and beta-catenin in sphere-cultured glioma cells. Treatment of GSCs with BHP significantly suppressed two fundamental characteristics of cancer stem cells: self-renewal and tumorigenicity. BHP treatment dramatically inhibited clone-forming ability at the single-cell level and suppressed in vivo tumor formation. BHP markedly inhibited both phosphoinositide 3-kinase/Akt and Ras/Raf-1/extracellular signal-regulated kinase signaling, which suggests that one or both of these pathways are involved in BHP-induced suppression of GSCs. In addition, treatment with BHP effectively sensitized GSCs to chemotherapy and radiotherapy. Taken together, these results indicate that BHP targets GSCs and enhances their sensitivity to anticancer treatments and suggest that BHP treatment may be useful for treating brain tumors by eliminating GSCs.
URI
http://molpharm.aspetjournals.org/content/82/3/400http://hdl.handle.net/20.500.11754/40960
ISSN
0026-895X
DOI
10.1124/mol.112.078402
Appears in Collections:
RESEARCH INSTITUTE[S](부설연구소) > THE RESEARCH INSTITUTE FOR NATURAL SCIENCES(자연과학연구소) > Articles
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