期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 19, 期 12, 页码 -出版社
MDPI
DOI: 10.3390/ijms19123813
关键词
beta-lapachone; breast-cancer stem-cell; DLGAP5; mammosphere; NQO1
资金
- National Research Foundation (NRF, Djejeon, Korea) - Ministry of Science, ICT and Future Planning [2016M3A9B6026771, 2014M3A9D5A01073598]
- National Research Foundation of Korea (NRF, Daejeon, Korea) - Ministry of Education [2017R1D1A1B03030844]
- National Research Foundation of Korea [2014M3A9D5A01073598, 2017R1D1A1B03030844] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Cancer stem cells (CSCs) exhibit self-renewal activity and give rise to other cell types in tumors. Due to the infinite proliferative potential of CSCs, drugs targeting these cells are necessary to completely inhibit cancer development. The beta-lapachone (bL) compound is widely used to treat cancer development; however, its effect on cancer stem cells remain elusive. Thus, we investigated the effect of bL on mammosphere formation using breast-cancer stem-cell (BCSC) marker-positive cells, MDA-MB-231. MDA-MB-231 cells, which are negative for reduced nicotinamide adenine dinucleotide phosphate (NAD(P)H):quinone oxidoreductase (NQO1) expression, were constructed to stably express NQO1 (NQO1 stable cells). The effect of bL on these cells was evaluated by wound healing and Transwell cell-culture chambers, ALDEFLUOR assay, and mammosphere formation assay. Here, we show that bL inhibited the proliferative ability of mammospheres derived from BCSC marker-positive cells, MDA-MB-231, in an NQO1-dependent manner. The bL treatment efficiently downregulated the expression level of BCSC markers cluster of differentiation 44 (CD44), aldehyde dehydrogenase 1 family member A1 (ALDH1A1), and discs large (DLG)-associated protein 5 (DLGAP5) that was recently identified as a stem-cell proliferation marker in both cultured cells and mammosphered cells. Moreover, bL efficiently downregulated cell proliferation and migration activities. These results strongly suggest that bL could be a therapeutic agent for targeting breast-cancer stem-cells with proper NQO1 expression.
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