ArticleCell cycle (Georgetown, Tex.)2012
Cyclosporin A inhibits colon cancer cell growth independently of the calcineurin pathway.
Article in Cell cycle (Georgetown, Tex.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 35 citations in OpenAlex.
- Shifting from pro-inflammatory to regulatory: L. reuteri postbiotics modulate IL-17/IL-10 axis in LPS-induced HT-29 IBD model.Archives of microbiology · 2025Article
- Select EZH2 inhibitors enhance viral mimicry effects of DNMT inhibition through a mechanism involving NFAT:AP-1 signaling.Science advances · 2024Article
- The potential role of cyclosporine A in cancer treatment: a comprehensive literature review.Contemporary oncology (Poznan, Poland) · 2024Review
- Differential dose-response effect of cyclosporine A in regulating apoptosis and autophagy markers in MCF-7 cells.Inflammopharmacology · 2023Article
- Cyclophilin A Inhibitors Suppress Proliferation and Induce Apoptosis of MKN45 Gastric Cancer Stem-like Cells by Regulating CypA/CD147-Mediated Signaling Pathway.International journal of molecular sciences · 2023Article
- RCAN1-mediated calcineurin inhibition as a target for cancer therapy.Molecular medicine (Cambridge, Mass.) · 2022Review
- The Effect of Cyclosporine A on Proteins Controlling Intracellular Calcium Concentration in Breast Cancer Cells.The Journal of membrane biology · 2022Article
- Calcium-sensing stromal interaction molecule 2 upregulates nuclear factor of activated T cells 1 and transforming growth factor-β signaling to promote breast cancer metastasis.Breast cancer research : BCR · 2019Article
- Effect of immunosuppression in miRNAs from extracellular vesicles of colorectal cancer and their influence on the pre-metastatic niche.Scientific reports · 2019Article
- Article
- Lessons to Learn From Low-Dose Cyclosporin-A: A New Approach for Unexpected Clinical Applications.Frontiers in immunology · 2019Review
- Antitumor pharmacotherapy of colorectal cancer in kidney transplant recipients.Therapeutic advances in medical oncology · 2019Review
- KRAS mutation leads to decreased expression of regulator of calcineurin 2, resulting in tumor proliferation in colorectal cancer.Oncogenesis · 2016Article
- ADAP and SKAP55 deficiency suppresses PD-1 expression in CD8+ cytotoxic T lymphocytes for enhanced anti-tumor immunotherapy.EMBO molecular medicine · 2015Article
- Peritoneal expression of Matrilysin helps identify early post-operative recurrence of colorectal cancer.Oncotarget · 2015Article
- Cyclosporine A and tacrolimus inhibit bladder cancer growth through down-regulation of NFATc1.Oncotarget · 2015Article
- Cyclophilin J is a novel peptidyl-prolyl isomerase and target for repressing the growth of hepatocellular carcinoma.PloS one · 2015Article
- Taking aim at Alzheimer's disease through the mammalian target of rapamycin.Annals of medicine · 2014Review
- Genes associated with metabolic syndrome predict disease-free survival in stage II colorectal cancer patients. A novel link between metabolic dysregulation and colorectal cancer.Molecular oncology · 2014Article
- Cutting through the complexities of mTOR for the treatment of stroke.Current neurovascular research · 2014Review
Corrections and comments
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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
Chronic inflammation is a risk factor for the development of colon cancer, providing genotoxic insults, growth and pro-angiogenic factors that can promote tumorigenesis and tumor growth. Immunomodulatory agents can interfere with the inflammation that feeds cancer, but their impact on the transformed cell is poorly understood. The calcium/calcineurin signaling pathway, through activation of NFAT, is essential for effective immune responses, and its inhibitors cyclosporin A (CsA) and FK506 are used in the clinics to suppress immunity. Moreover, the kinases GSK3β and mTOR, modulated by PI-3K/Akt, can inhibit NFAT activity, suggesting a cross-talk between the calcium and growth factor signaling pathways. Both NFAT and mTOR activity have been associated with tumorigenesis. We therefore investigated the impact of calcineurin and PI-3K/mTOR inhibition in growth of human colon carcinoma cells. We show that despite the efficient inhibition of NFAT1 activity, FK506 promotes tumor growth, whereas CsA inhibits it due to a delay in cell cycle progression and induction of necroptosis. We found NFκB activation and mTORC1 activity not to be altered by CsA or FK506. Similarly, changes to mitochondrial homeostasis were equivalent upon treatment with these drugs. We further show that, in our model, NFAT1 activation is not modulated by PI3K/mTOR. We conclude that CsA slows cell cycle progression and induces necroptosis of human carcinoma cell lines in a TGFβ-, NFAT-, NFκB- and PI3K/mTOR-independent fashion. Nevertheless, our data suggest that CsA, in addition to its anti-inflammatory capacity, may target transformed colon and esophagus carcinoma cells without affecting non-transformed cells, promoting beneficial tumoristatic effects.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.