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The efficacy of radiotherapy in ATL needs enhancement with radiosensitizing agents. This study investigated whether umbelliprenin (UMB) could improve the therapeutic effects of ionizing radiation (IR) in ATL cells. UMB, a naturally occurring prenylated coumarin, exhibits anticancer properties and has shown synergistic effects when combined with chemotherapeutic drugs. Despite this promising profile, there is a notable lack of research on its potential combinatorial effects with IR, particularly for ATL treatment. UMB was extracted from\u00a0 Ferula persica\u00a0using thin layer chromatography. MT-2 cells were treated with UMB alone and in combination with various doses of IR, and cell proliferation was assessed via alamarBlue assay. Flow cytometry with annexin V and PI staining was conducted, and candidate gene expression was analyzed by qPCR.\u00a0 In silico\u00a0analysis involved identifying pathogenic targets of ATL, constructing protein-protein interaction\u00a0(PPI) networks, and evaluating CDK6 expression in MT-2 cells. Molecular docking was used to determine the interaction between UMB and CDK6. The alamarBlue assay and flow cytometry showed that pretreating ATL cells with UMB significantly ( p\u00a0&lt; .0001) enhanced anti-proliferative effects of IR. The combination index indicated a synergistic effect between UMB and IR. qPCR revealed significant ( p\u00a0&lt; .0001) downregulation of\u00a0 CD44, CDK6, c-MYC, and\u00a0 cFLIPL, and overexpression of\u00a0 cFLIPS. Computational analysis identified CDK6 as a hub gene in the PPI network, and CDK6 overexpression was confirmed in MT-2 cells. Molecular docking revealed a favorable binding interaction between UMB and the ATP-binding site of CDK6, with a JAMDA score of\u00a0\u22122.131, surpassing the control selonsertib. The current study provides evidence that UMB enhances the anti-proliferative effects of IR on ATL cells, and highlights the significance of targeting CDK6 in combinatorial approaches.<\/jats:p>","DOI":"10.1177\/03946320241287873","type":"journal-article","created":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T11:52:29Z","timestamp":1727178749000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Umbelliprenin improved anti-proliferative effects of ionizing radiation on adult T-cell leukemia\/lymphoma cells via interaction with CDK6; an\n                    <i>in vitro<\/i>\n                    and\n                    <i>in silico<\/i>\n                    study"],"prefix":"10.1177","volume":"38","author":[{"given":"Keyhan","family":"Ebrahimi","sequence":"first","affiliation":[{"name":"Cancer Molecular Pathology Research Center, Department of Hematology, Faculty of Medicine, Mashhad University of 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Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Houshang","family":"Rafatpanah","sequence":"additional","affiliation":[{"name":"Immunology Research Center, Inflammation and inflammatory Diseases Division, Mashhad University of Medical Sciences, Mashhad, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehrdad","family":"Iranshahi","sequence":"additional","affiliation":[{"name":"Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1889-0964","authenticated-orcid":false,"given":"Fatemeh B","family":"Rassouli","sequence":"additional","affiliation":[{"name":"Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, 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