ArticleCellular oncology (Dordrecht, Netherlands)2018
A2B adenosine receptor agonist induces cell cycle arrest and apoptosis in breast cancer stem cells via ERK1/2 phosphorylation.
Article in Cellular oncology (Dordrecht, Netherlands), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
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- Purinergic system in cancer stem cells.Purinergic signalling · 2025Review
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- Adenosine receptors in breast cancer.Molecular biology reports · 2024Review
- A2B Adenosine Receptor in Idiopathic Pulmonary Fibrosis: Pursuing Proper Pit Stop to Interfere with Disease Progression.International journal of molecular sciences · 2023Review
- The adenosine-A2a receptor regulates the radioresistance of gastric cancer via PI3K-AKT-mTOR pathway.International journal of clinical oncology · 2022Article
- Current Adenosinergic Therapies: What Do Cancer Cells Stand to Gain and Lose?International journal of molecular sciences · 2021Review
- Autocrine and paracrine purinergic signaling in the most lethal types of cancer.Purinergic signalling · 2021Review
- Mechanism of inositol-requiring enzyme 1-alpha inhibition in endoplasmic reticulum stress and apoptosis in ovarian cancer cells.Journal of cell communication and signaling · 2020Article
- Cockle Shell-Derived Aragonite CaCOInternational journal of molecular sciences · 2020Article
- Inhibition of the Adenosinergic Pathway in Cancer Rejuvenates Innate and Adaptive Immunity.International journal of molecular sciences · 2019Review
- MicroRNA‑125a‑5p controls the proliferation, apoptosis, migration and PTEN/MEK1/2/ERK1/2 signaling pathway in MCF‑7 breast cancer cells.Molecular medicine reports · 2019Article
- Purine-Metabolising Enzymes and Apoptosis in Cancer.Cancers · 2019Review
- Targeting Adenosine in Cancer Immunotherapy to Enhance T-Cell Function.Frontiers in immunology · 2019Review
- Immunometabolic Dysfunction of Natural Killer Cells Mediated by the Hypoxia-CD73 Axis in Solid Tumors.Frontiers in molecular biosciences · 2019Review
- Galectin-9 induces apoptosis in OVCAR-3 ovarian cancer cell through mitochondrial pathway.Research in pharmaceutical sciences · 2018Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeIt has been reported that cancer stem cells (CSCs) may play a crucial role in the development, recurrence and metastasis of breast cancer. Targeting signaling pathways in CSCs is considered to be a promising strategy for the treatment of cancer. Here, we investigated the role of the A2B adenosine receptor (A2BAR) and its associated signaling pathways in governing the proliferation and viability of breast cancer cell line derived CSCs.
methodsCSCs were isolated from the breast cancer cell lines MCF-7 and MDA-MB-231 using a mammosphere assay. The effect of the A2BAR agonist BAY606583 on cell proliferation was evaluated using XTT and mammosphere formation assays, respectively. Apoptosis was assessed using Annexin-V staining and cell cycle analyses were performed using flow cytometry. The expression levels of Bax, Bcl-2, cyclin-D1, CDK-4 and (phosphorylated) ERK1/2 were assessed using Western blotting.
resultsOur data revealed that the breast cancer cell line derived mammospheres were enriched for CSCs. We also found that A2BAR stimulation with its agonist BAY606583 inhibited mammosphere formation and CSC viability. In addition, we found that the application of BAY606583 led to CSC cell cycle arrest and apoptosis through the cyclin-D1/Cdk-4 and Bax/Bcl-2 pathways, respectively. Notably, we found that BAY606583 significantly down-regulated ERK1/2 phosphorylation in the breast cancer cell line derived CSCs.
conclusionsFrom our results we conclude that A2BAR induces breast CSC cell cycle arrest and apoptosis through downregulation of the ERK1/2 cascade. As such, A2BAR may be considered as a novel target for the treatment of breast cancer.
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