ArticlePediatric blood & cancer2013
FTY720 inhibits tumor growth and enhances the tumor-suppressive effect of topotecan in neuroblastoma by interfering with the sphingolipid signaling pathway.
Article in Pediatric blood & cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 32 citations in OpenAlex.
- PP2A Activation as a Senotherapeutic in Neuroblastoma.Cancers · 2026Article
- Opaganib Downregulates N-Myc Expression and Suppresses In Vitro and In Vivo Growth of Neuroblastoma Cells.Cancers · 2024Article
- Targeting sphingosine kinase 1 in p53KO thymic lymphoma.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- β3-adrenergic receptor on tumor-infiltrating lymphocytes sustains IFN-γ-dependent PD-L1 expression and impairs anti-tumor immunity in neuroblastoma.Cancer gene therapy · 2023Article
- Metagenomic and metabolomic analysis of changes in intestinal contents of rainbow trout (Frontiers in microbiology · 2023Article
- Multiple approaches to repurposing drugs for neuroblastoma.Bioorganic & medicinal chemistry · 2022Article
- Article
- Differential Expression of the Sphingolipid Pathway Is Associated with Sensitivity to the PP2A Activator FTY720 in Colorectal Cancer Cell Lines.Journal of clinical medicine · 2021Article
- Role of Sphingosine Kinase in Type 2 Diabetes Mellitus.Frontiers in endocrinology · 2020Review
- Review
- Investigation of PP2A and Its Endogenous Inhibitors in Neuroblastoma Cell Survival and Tumor Growth.Translational oncology · 2019Article
- FTY720 enhances the anti-tumor activity of carboplatin and tamoxifen in a patient-derived xenograft model of ovarian cancer.Cancer letters · 2018Article
- Sphingadienes show therapeutic efficacy in neuroblastoma in vitro and in vivo by targeting the AKT signaling pathway.Investigational new drugs · 2018Article
- Sphingolipid metabolism and drug resistance in ovarian cancer.Cancer drug resistance (Alhambra, Calif.) · 2018Article
- Article
- Sphingosine-1-Phosphate Receptor-1 Promotes Environment-Mediated and Acquired Chemoresistance.Molecular cancer therapeutics · 2017Article
- The emerging role of FTY720 (Fingolimod) in cancer treatment.Oncotarget · 2016Review
- FTY720 (Fingolimod) sensitizes hepatocellular carcinoma cells to sorafenib-mediated cytotoxicity.Pharmacology research & perspectives · 2015Article
- The antineoplastic properties of FTY720: evidence for the repurposing of fingolimod.Journal of cellular and molecular medicine · 2015Review
- Antitumor Activity of a Novel Sphingosine-1-Phosphate 2 Antagonist, AB1, in Neuroblastoma.The Journal of pharmacology and experimental therapeutics · 2015Article
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundNeuroblastoma (NB) is the most common extra-cranial solid tumor in childhood. Poor outcomes for children with advanced disease underscore the need for novel therapeutic strategies. FTY720, an immunomodulating drug approved for multiple sclerosis, has been investigated in oncology with promising preclinical activities. To date, its effect in NB has not been explored. Herein we describe our preclinical experience with FTY720, alone or in combination with topotecan, and its putative mechanism of action in NB. PROCEDURE: MTT assay was performed to assess the effect of FTY720 on cell viability. A NB xenograft model was employed to assess the efficacy of FTY720 on tumor growth. Quantitative real-time PCR and Western blot were employed to determine changes of mRNA and protein expression, respectively. Liquid chromatography/tandem mass spectrometry was used to measure sphingolipid levels.
resultsFTY720, but not FTY720-P induced NB cell death. FTY720 inhibited the growth of NB xenografts and enhanced the tumor-suppressive effect of topotecan both in vitro and in vivo. FTY720 significantly inhibited sphingosine kinase 2 (SphK2) mRNA and protein expression in NB cells. Pro-apoptotic sphingosine levels were increased in NB cells and NB xenografts treated with FTY720. FTY720-induced cell death was caspase-independent and involved the dephosphorylation of Akt and BAD at Ser136.
conclusionsOur data demonstrate that FTY720 has potent preclinical anti-cancer activity in NB. Its unique death signaling mechanism, interference with the sphingolipid pathway, acts cooperatively with that of topotecan, suggesting that FTY720 related molecules may be useful in NB treatment.
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