{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T19:21:13Z","timestamp":1762543273420,"version":"3.40.5"},"reference-count":50,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T00:00:00Z","timestamp":1599091200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>New effective therapeutic strategies for human T\u2010cell leukemia virus type 1 (HTLV\u20101)\u2010driven adult T\u2010cell leukemia (ATL) are required because of resistance to chemotherapeutic agents. Here, we aimed to determine the therapeutic efficacy of a dual phosphoinositide 3 kinase (PI3K)\/histone deacetylase (HDAC) inhibitor, CUDC\u2010907.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cell viability, cell cycle progression, and apoptotic events were examined by WST\u20108 assay, flow cytometry, and Hoechst 33342 staining. Caspase activity was determined using Calorimetric Caspase Assay kits. Immunoblotting and electrophoretic mobility shift assay were used to assess the intracellular signaling cascades.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The combination of PI3K inhibitor BKM120 and HDAC inhibitor LBH589 resulted in a synergistic cytotoxic effect in HTLV\u20101\u2010infected T cells. CUDC\u2010907 was more efficacious than BKM120 and LBH589. It induced G<jats:sub>1<\/jats:sub> cell cycle arrest with downregulation of cyclin D1\/D2, CDK4\/6, c\u2010Myc, and phosphorylated retinoblastoma protein expression. Apoptosis was induced via caspase\u20103\/8\/9 activation along with downregulation of Bcl\u2010X<jats:sub>L<\/jats:sub>, Bcl\u20102, XIAP, survivin, and cIAP1\/2, and upregulation of Bax and Bak. Histone H3 acetylation, H2AX activation, Hsp27 phosphorylation, and Hsp70 and Hsp27 upregulation were observed after treatment. CUDC\u2010907 suppressed Akt, NF\u2010\u03baB, and AP\u20101 by downregulating phosphorylated and\/or total Akt, IKK\u03b1\/\u03b2, RelA, JunB, and JunD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>CUDC\u2010907 may be a potential therapeutic agent for ATL.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ejh.13508","type":"journal-article","created":{"date-parts":[[2020,8,12]],"date-time":"2020-08-12T03:39:24Z","timestamp":1597203564000},"page":"763-772","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The role of CUDC\u2010907, a dual phosphoinositide\u20103 kinase and histone deacetylase inhibitor, in inhibiting proliferation of adult T\u2010cell leukemia"],"prefix":"10.1111","volume":"105","author":[{"given":"Chie","family":"Ishikawa","sequence":"first","affiliation":[{"name":"Department of Microbiology and Oncology Graduate School of Medicine University of the Ryukyus Nishihara Okinawa 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