Effects of celecoxib and L-NAME on apoptosis and cell cycle ofMCF-7 CD44+/CD24-/low subpopulation
| Autor: | Seyed Nasser Ostad, Melody Vatankhah, Shima Aliebrahimi, Maryam Majdzadeh |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Programmed cell death Cell cycle checkpoint Physiology Biology Microbiology 03 medical and health sciences 0302 clinical medicine Cancer stem cell Genetics medicine skin and connective tissue diseases Molecular Biology integumentary system CD44 Cell Biology Cell cycle Celecoxib L-NAME cancer stem cell-like cells CD44+CD24-/low cytotoxicity 030104 developmental biology Apoptosis Cell culture 030220 oncology & carcinogenesis Celecoxib biology.protein Cancer research General Agricultural and Biological Sciences medicine.drug |
| Zdroj: | Volume: 41, Issue: 5 826-934 Turkish Journal of Biology |
| ISSN: | 1300-0152 1303-6092 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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