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

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 ϩ cell population. Treatment with BHP also suppressed expression of the stemness-regulating transcription factors Sox2, Notch2, and ␤-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 cloneforming 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.

Enrichment and characterization of cancer stem-like cells from a cervical cancer cell line

“…Previous studies indicated that a small population of CSCs appear to be responsible for tumor initiation and progression and also for the resistance to conventional treatment (18,19). Recently, isolation, identification and selective eradication of CSCs using targeted drugs have become a major focus in basic and clinical cancer studies (20,21). Therefore, for investigating and developing agents targeting CSCs for cancer therapeutics, a reliable model of CSCs is crucial for basic and preclinical studies.…”

CD44⁺/CD24⁺-Expressing Cervical Cancer Cells and Radioresistant Cervical Cancer Cells Exhibit Cancer Stem Cell Characteristics

“…Increasing scientific evidence supports the notion that CSCs are responsible for the cancer's resistance to chemoradiation therapy as well as for its metastatic properties, which lead to poor prognosis for numerous human cancers, including cervical cancer [17][18][19]. To date, methods of identifying CSCs has already become hot points in basic cancer research [20], but no universal markers are currently used for the isolation and identification of CSCs in any particular cancer. This study showed that radiation-resistant cervical cancer cells obtained characteristics of CSCs, showing a high expression of apoptosis inhibitory protein surviving, anti-apoptotic protein Bcl-2, and stem cell markers (Oct4, ABCG2, CD24 and CD44).…”