https://scholars.lib.ntu.edu.tw/handle/123456789/634497
標題: | Discovery of New Glucose Uptake Inhibitors as Potential Anticancer Agents by Non-Radioactive Cell-Based Assays | 作者: | Hung, Hsueh-Chih Li, Li-Cheng JIH-HWA GUH FAN-LU KUNG LIH-CHING HSU |
關鍵字: | 2-NBDG; GLUT1 inhibitors; anticancer; breast and ovarian cancer; glucose uptake assays | 公開日期: | 21-十一月-2022 | 卷: | 27 | 期: | 22 | 起(迄)頁: | 8106 | 來源出版物: | Molecules (Basel, Switzerland) | 摘要: | Tumor cells rely on aerobic glycolysis to support growth and survival, thus require more glucose supply. Glucose transporters GLUTs, primarily GLUT1, are overexpressed in various cancers. Targeting GLUTs has been regarded as a promising anticancer strategy. In this study, we first evaluated 75 potential GLUT1 inhibitors obtained from virtual screening of the NCI chemical library by a high-throughput cell-based method using a fluorescent glucose analogue 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxy-d-glucose (2-NBDG) in COS-7 and SKOV3 cells that express high levels of GLUT1. Four compounds, #12, #16, #43 and #69, that significantly inhibited glucose uptake were further evaluated using flow cytometry directly measuring 2-NBDG uptake at the single-cell level and a Glucose Uptake-GloTM assay indirectly measuring 2-deoxy-d-glucose uptake in SKOV3, COS-7 or MCF-7 cells. The inhibitory effect on cancer cell growth was also determined in SKOV3 and MCF-7 cells, and #12 exhibited the best growth inhibitory effect equivalent to a known GLUT1 inhibitor WZB117. Although the anticancer effect of the identified potential GLUT1 inhibitors was moderate, they may enhance the activity of other anticancer drugs. Indeed, we found that #12 synergistically enhanced the anticancer activity of metformin in SKOV3 ovarian cancer cells. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/634497 | ISSN: | 1420-3049 | DOI: | 10.3390/molecules27228106 |
顯示於: | 藥學系 |
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