TY - JOUR T1 - A New 2-Pyrone Derivative, 5-Bromo-3-(3-Hydroxyprop-1-Ynyl)-2H-Pyran-2-One, Suppresses Stemness in Glioma Stem-Like Cells JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.112.078402 SP - mol.112.078402 AU - Rae-Kwon Kim AU - Min-Jung Kim AU - Chang-Hwan Yoon AU - Eun-Jung Lim AU - Ki-Chun Yoo AU - Ga-Haeng Lee AU - Young-Heon Kim AU - Hyeonmi Kim AU - Yeung Bae Jin AU - Yoon-Jin Lee AU - Cheon-Gyu Cho AU - Yeong Seok Oh AU - Myung Chan Gye AU - Yongjoon Suh AU - Su-Jae Lee Y1 - 2012/05/30 UR - http://molpharm.aspetjournals.org/content/early/2012/05/30/mol.112.078402.abstract N2 - Glioma cells with stem cell properties, termed glioma stem-like cells (GSCs) have been linked to tumor formation, maintenance and progression, and are also responsible for the failure of chemo- and radiotherapy. Because conventional glioma treatments often fail to eliminate GSCs completely, residual surviving GSCs are able to repopulate the tumor. Thus, compounds that target GSCs could be helpful in overcoming resistance to anticancer treatments in human brain tumors. In this study, we show that 5-bromo-3-(3-hydroxyprop-1-ynyl)-2H-pyran-2-one (BHP), a new 2-pyrone derivative, suppresses 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 β-catenin in sphere-cultured glioma cells. Moreover, 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 PI3K-AKT and Ras-Raf-1-ERK signaling, suggesting that either or both of these pathways are involved in BHP-induced suppression of GSCs. In addition, treatment with BHP effectively sensitized GSCs to chemo- and radiotherapy. Taken together, these results indicate that BHP targets GSCs and enhances their sensitivity to anticancer treatments, suggesting that BHP treatment may be useful for treating brain tumors by eliminating GSCs. ER -