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Apoptosis and cell cycle regulatory effects of adenosine by modulation of GLI-1 and ERK1/2 pathways in CD44+ and CD24− breast cancer stem cells

Jafari, S.M. and Joshaghani, H.R. and Panjehpour, M. and Aghaei, M. and Zargar Balajam, N. (2017) Apoptosis and cell cycle regulatory effects of adenosine by modulation of GLI-1 and ERK1/2 pathways in CD44+ and CD24− breast cancer stem cells. Cell Proliferation, 50 (4).

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Abstract

Objectives: Breast cancer stem cells (CSCs) are a small population of tumour cells with the ability of self-renewal and resistance to chemotherapy. Targeting CSCs is a promising strategy for treatment of cancer. A recent study demonstrated that adenosine receptor agonists inhibit glioblastoma CSCs proliferation. At present, the effect of adenosine on breast CSCs has not been reported. Therefore, this study was designed to evaluate the effect of adenosine and its signalling pathways in breast CSCs. Materials and methods: Anti-proliferative effect of adenosine on breast CSCs was evaluated by mammosphere formation and MTS assay. The effect of adenosine on cell cycle progression was examined using flow cytometry. Detection of apoptosis was conducted by Annexin V-FITC. The expression levels of cell cycle and apoptosis regulatory proteins as well as ERK1/2, and GLI-1 were measured by Western blot. Results: Adenosine reduced CSCs population and mammosphere formation in breast CSCs. Adenosine induced G1 cell cycle arrest in breast CSCs in conjunction with a marked down-regulation of cyclin D1 and CDK4. Adenosine also induced apoptosis by regulation of Bax/Bcl-2 ratio, mitochondrial membrane potential depletion and activation of caspase-6. Moreover, adenosine inhibited ERK1/2 phosphorylation and GLI-1 protein expression. Conclusions: These findings indicated that adenosine induces cell cycle arrest and apoptosis through inhibition of GLI-1 and ERK1/2 pathways in breast CSCs. © 2017 John Wiley & Sons Ltd

Item Type: Article
Additional Information: cited By 0
Uncontrolled Keywords: adenosine; caspase 6; cyclin D1; cyclin dependent kinase 4; Hermes antigen; mitogen activated protein kinase 1; mitogen activated protein kinase 3; protein Bax; protein bcl 2; transcription factor Gli1; adenosine; caspase 6; CCND1 protein, human; CD24 antigen; CD44 protein, human; CDK4 protein, human; cyclin D1; cyclin dependent kinase 4; GLI1 protein, human; Hermes antigen; protein Bax; protein bcl 2; transcription factor Gli1, antiproliferative activity; apoptosis; Article; breast cancer; cancer stem cell; cell cycle progression; cell cycle regulation; controlled study; down regulation; enzyme activation; enzyme phosphorylation; flow cytometry; G1 phase cell cycle checkpoint; MCF-7 cell line; MDA-MB-231 cell line; mitochondrial membrane potential; MTS assay; protein expression; regulatory mechanism; signal transduction; Western blotting; apoptosis; breast tumor; cancer stem cell; cytology; drug effects; female; human; MAPK signaling; metabolism; pathology; tumor cell line, Adenosine; Antigens, CD24; Antigens, CD44; Apoptosis; bcl-2-Associated X Protein; Breast Neoplasms; Caspase 6; Cell Line, Tumor; Cyclin D1; Cyclin-Dependent Kinase 4; Down-Regulation; Female; G1 Phase Cell Cycle Checkpoints; Humans; MAP Kinase Signaling System; MCF-7 Cells; Membrane Potential, Mitochondrial; Neoplastic Stem Cells; Proto-Oncogene Proteins c-bcl-2; Zinc Finger Protein GLI1
Subjects: مقالات نمایه شده محققین دانشگاه در سایت ,Web of Science ,Scopus
Divisions: UNSPECIFIED
Depositing User: GOUMS
Date Deposited: 27 Dec 2017 07:29
Last Modified: 27 Dec 2017 07:29
URI: http://eprints.goums.ac.ir/id/eprint/9482

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