ArticleJournal of translational medicine2017
FTY720 inhibits mesothelioma growth in vitro and in a syngeneic mouse model.
Article in Journal of translational medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- Protein phosphatase 2 phosphatase activator (PTPA) promotes oncogene-induced senescence and carboplatin response in human malignant pleural mesothelioma cells.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Promising Molecular Targets in Pharmacological Therapy for Neuronal Damage in Brain Injury.Antioxidants (Basel, Switzerland) · 2023Review
- SET levels contribute to cohesion fatigue.Molecular biology of the cell · 2021Article
- Mouse models for mesothelioma drug discovery and development.Expert opinion on drug discovery · 2021Review
- Targeting the Sphingosine Kinase/Sphingosine-1-Phosphate Signaling Axis in Drug Discovery for Cancer Therapy.Cancers · 2021Review
- Implications of Sphingolipids on Aging and Age-Related Diseases.Frontiers in aging · 2021Review
- Druggable Sphingolipid Pathways: Experimental Models and Clinical Opportunities.Advances in experimental medicine and biology · 2020Review
- Redox inhibition of protein phosphatase PP2A: Potential implications in oncogenesis and its progression.Redox biology · 2019Review
- Protein phosphatase 2A as a therapeutic target in inflammation and neurodegeneration.Pharmacology & therapeutics · 2019Review
- Review
- PP2ACα of Alveolar Macrophages Is a Novel Protective Factor for LPS-Induced Acute Respiratory Distress Syndrome.Inflammation · 2019Article
- Multiple Sclerosis and Cancer: The Ying-Yang Effect of Disease Modifying Therapies.Frontiers in immunology · 2019Review
- Investigation of PP2A and Its Endogenous Inhibitors in Neuroblastoma Cell Survival and Tumor Growth.Translational oncology · 2019Article
- FTY720 Decreases Tumorigenesis in Group 3 Medulloblastoma Patient-Derived Xenografts.Scientific reports · 2018Article
- More than Just an Immunosuppressant: The Emerging Role of FTY720 as a Novel Inducer of ROS and Apoptosis.Oxidative medicine and cellular longevity · 2018Review
- A genome-wide screen for FTY720-sensitive mutants reveals genes required for ROS homeostasis.Microbial cell (Graz, Austria) · 2017Article
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundMalignant mesothelioma (MM) is a very aggressive type of cancer, with a dismal prognosis and inherent resistance to chemotherapeutics. Development and evaluation of new therapeutic approaches is highly needed. Immunosuppressant FTY720, approved for multiple sclerosis treatment, has recently raised attention for its anti-tumor activity in a variety of cancers. However, its therapeutic potential in MM has not been evaluated yet.
methodsCell viability and anchorage-independent growth were evaluated in a panel of MM cell lines and human mesothelial cells (HM) upon FTY720 treatment to assess in vitro anti-tumor efficacy. The mechanism of action of FTY720 in MM was assessed by measuring the activity of phosphatase protein 2A (PP2A)-a major target of FTY720. The binding of the endogenous inhibitor SET to PP2A in presence of FTY720 was evaluated by immunoblotting and immunoprecipitation. Signaling and activation of programmed cell death were evaluated by immunoblotting and flow cytometry. A syngeneic mouse model was used to evaluate anti-tumor efficacy and toxicity profile of FTY720 in vivo.
resultsWe show that FTY720 significantly suppressed MM cell viability and anchorage-independent growth without affecting normal HM cells. FTY720 inhibited the phosphatase activity of PP2A by displacement of SET protein, which appeared overexpressed in MM, as compared to HM cells. FTY720 promoted AKT dephosphorylation and Bcl-2 degradation, leading to induction of programmed cell death, as demonstrated by caspase-3 and PARP activation, as well as by cytochrome c and AIF intracellular translocation. Moreover, FTY720 administration in vivo effectively reduced tumor burden in mice without apparent toxicity.
conclusionsOur preclinical data indicate that FTY720 is a potentially promising therapeutic agent for MM treatment.
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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.