期刊
TURKISH JOURNAL OF BIOLOGY
卷 41, 期 5, 页码 826-834出版社
Tubitak Scientific & Technological Research Council Turkey
DOI: 10.3906/biy-1703-101
关键词
Celecoxib; L-NAME; cancer stem cell-like cells; CD44(+)CD24(-/low); cytotoxicity
类别
资金
- Tehran University of Medical Science [91-01-33-18344]
Recent studies have reported that cancer stem cells (CSCs) play a pivotal role in treatment failure, causing cancer recurrence. Here, we investigated the effects of L-NAME (an iNOS inhibitor) and celecoxib (a selective COX-2 inhibitor) on CSC-like cells (CSC-LCs) and their parental cells. Breast CSC-LCs derived from the MCF-7 cell line were sorted and characterized with the CD44(+)/CD24(-/low) phenotype. After isolation, the percentage of the subpopulation expressing CD44(+)/CD24(-/low) biomarkers increased considerably from 0.96% to 28.6%. Use of L-NAME and celecoxib showed antiproliferative activity towards both MCF-7 and CSC-LCs. Although celecoxib enhanced apoptotic cell death, the CSC-LC population was more resistant than parental cells. Moreover, L-NAME was less effective at inducing apoptosis, suggesting an involvement of different mechanisms of cell death. L-NAME caused cell cycle arrest in the S-phase in CSC-LCs, while celecoxib induced G0/G1 arrest in CSC-LCs and their parental cells. Immunocytochemistry results demonstrated that L-NAME had a similar potency to attenuate iNOS expression in MCF-7 and CSC-LCs; however, celecoxib reduced COX-2 expression in MCF-7 cells. The results show the crucial role of NOS and COX-2 in the maintenance of CD44(+)/CD24(-/low) breast CSC-LCs and suggest that L-NAME and celecoxib could have clinical implication in combination therapy.
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