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GBM cells exhibit cell cycle disruption and treatment resistance, remarking an urgent need for newer treatments. Fingolimod, a sphingosine\u20101\u2010phosphate receptor modulator, has been reported to have anti\u2010cancer effects. This study investigated the therapeutic potentials of fingolimod in rat C6 cells and pursued the involved mechanism(s). Cell survival, proliferation, migration, and morphology of fingolimod\u2010treated C6 cells were evaluated using MTT, soft\u2010agar colony formation, wound\u2010healing, and Giemsa staining assays. Apoptosis was investigated through acridine orange\/ethidium bromide (AO\/EB) and annexin V staining, and flow cytometry analysed the cell cycle. Quantitative reverse transcription PCR and western blotting were used to evaluate gene and protein expressions. An intracranial C6 rat model validated the anti\u2010tumour effect of fingolimod. Fingolimod significantly reduced the survival and colonies of the C6 cells and delayed their gap closure. Cell shrinkage coupled with AO\/EB and PI staining of the fingolimod\u2010treated cells indicated apoptosis, subsequently confirmed by measuring the expression levels of the candidate genes involved in apoptosis and cell cycle, such as Bax\/Bcl2, P53, Cytochrome C and Caspases 9\/3, Fas, Fadd, Tnfrsf1a, Cdkn1a, and Ccnd1, at RNA and protein levels, indicating both extrinsic and mitochondrial apoptosis and cell cycle arrest at sub\u2010G1 phase in fingolimod\u2010treated cells. Furthermore, treating rats bearing intracranial C6 tumours with fingolimod led to significant suppression of intracranial tumour growth. Based on our findings, cell cycle arrest and apoptosis contribute to fingolimod antitumor effects.<\/jats:p>","DOI":"10.1111\/1440-1681.70012","type":"journal-article","created":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T03:34:36Z","timestamp":1733196876000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Fingolimod Inhibits <scp>C6<\/scp> Rat Glioma Proliferation and Migration, Induces Sub\u2010<scp>G1<\/scp> Cell Cycle Arrest, Mitochondrial and Extrinsic Apoptosis In\u00a0Vitro and Reduces Tumour Growth In\u00a0Vivo"],"prefix":"10.1111","volume":"52","author":[{"given":"Safura","family":"Pournajaf","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Medical Sciences Tarbiat Modares University  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nastaran","family":"Afsordeh","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medical Sciences Tarbiat Modares University  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadi","family":"Bayat","sequence":"additional","affiliation":[{"name":"Biochemical Neuroendocrinology Montreal Clinical Research Institute (IRCM), affiliated to the Division of Experimental Medicine, Faculty of Medicine and Health Sciences, McGill University  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1158-801X","authenticated-orcid":false,"given":"Mohammad Hossein","family":"Pourgholami","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medical Sciences Tarbiat Modares University  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/nop\/npac015"},{"key":"e_1_2_9_3_1","volume-title":"StatPearls","author":"Kanderi T.","year":"2022"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-14-0275"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.117.014944"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-023-02502-9"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2020.100926"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.22691"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.7145"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.807639"},{"issue":"4","key":"e_1_2_9_11_1","first-page":"1039","article-title":"Sphingosine\u20101\u2010Phosphate Analogue FTY720 Exhibits a Potent Anti\u2010Proliferative Effect on Glioblastoma Cells","volume":"57","author":"Kolodziej M. 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