{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:00:17Z","timestamp":1787313617974,"version":"build-2736575974"},"reference-count":51,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,4,13]],"date-time":"2016-04-13T00:00:00Z","timestamp":1460505600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007369","name":"Fukuoka Foundation for Sound Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007369","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005738","name":"Central Research Institute, Fukuoka University","doi-asserted-by":"publisher","award":["147107"],"award-info":[{"award-number":["147107"]}],"id":[{"id":"10.13039\/501100005738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science, and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:p>\n                    Adult T\u2010cell leukemia\/lymphoma (\n                    <jats:styled-content style=\"fixed-case\">ATL<\/jats:styled-content>\n                    ), an aggressive T\u2010cell malignancy that develops after long\u2010term infection with human T\u2010cell leukemia virus (\n                    <jats:styled-content style=\"fixed-case\">HTLV<\/jats:styled-content>\n                    \u20101), requires new treatments. Drug repositioning, reuse of a drug previously approved for the treatment of another condition to treat\n                    <jats:styled-content style=\"fixed-case\">ATL<\/jats:styled-content>\n                    , offers the possibility of reduced time and risk. Among clinically available angiotensin\n                    <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>\n                    receptor blockers, telmisartan is well known for its unique ability to activate peroxisome proliferator\u2010activated receptor\u2010\u03b3, which plays various roles in lipid metabolism, cellular differentiation, and apoptosis. Here, telmisartan reduced cell viability and enhanced apoptotic cells via caspase activation in\n                    <jats:italic>ex vivo<\/jats:italic>\n                    peripheral blood monocytes from asymptomatic\n                    <jats:styled-content style=\"fixed-case\">HTLV<\/jats:styled-content>\n                    \u20101 carriers (\n                    <jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>\n                    s) or via caspase\u2010independent cell death in acute\u2010type\n                    <jats:styled-content style=\"fixed-case\">ATL<\/jats:styled-content>\n                    , which has a poor prognosis. Telmisartan also induced significant growth inhibition and apoptosis in leukemia cell lines via caspase activation, whereas other angiotensin\n                    <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>\n                    receptor blockers did not induce cell death. Interestingly, telmisartan increased the\n                    <jats:styled-content style=\"fixed-case\">LC<\/jats:styled-content>\n                    3\u2010\n                    <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>\n                    \u2010enriched protein fraction, indicating autophagosome accumulation and autophagy. Thus, telmisartan simultaneously caused caspase activation and autophagy. A hypertension medication with antiproliferation effects on primary and leukemia cells is intriguing. Patients with an early diagnosis of\n                    <jats:styled-content style=\"fixed-case\">ATL<\/jats:styled-content>\n                    are generally monitored until the disease progresses; thus, suppression of progression from\n                    <jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>\n                    and indolent\n                    <jats:styled-content style=\"fixed-case\">ATL<\/jats:styled-content>\n                    to acute\n                    <jats:styled-content style=\"fixed-case\">ATL<\/jats:styled-content>\n                    is important. Our results suggest that telmisartan is highly effective against primary cells and leukemia cell lines in caspase\u2010dependent and \u2010independent manners, and its clinical use may suppress acute transformation and improve prognosis of patients with this mortal disease. This is the first report demonstrating a cell growth\u2010inhibitory effect of telmisartan in fresh peripheral blood mononuclear cells from leukemia patients.\n                  <\/jats:p>","DOI":"10.1002\/2211-5463.12055","type":"journal-article","created":{"date-parts":[[2016,3,18]],"date-time":"2016-03-18T22:15:03Z","timestamp":1458339303000},"page":"442-460","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Angiotensin\n                    <scp>II<\/scp>\n                    type 1 receptor blocker telmisartan induces apoptosis and autophagy in adult T\u2010cell leukemia cells"],"prefix":"10.1002","volume":"6","author":[{"given":"Tomohiro","family":"Kozako","sequence":"first","affiliation":[{"name":"Department of Biochemistry Faculty of Pharmaceutical Sciences Fukuoka University Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhei","family":"Soeda","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Faculty of Pharmaceutical Sciences Fukuoka University Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Yoshimitsu","sequence":"additional","affiliation":[{"name":"Department of Hematology and Immunology Kagoshima University Hospital Japan"},{"name":"Division of Hematology and Immunology School of Medical and Dental Sciences Center for Chronic Viral Diseases Graduate Kagoshima University Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomichi","family":"Arima","sequence":"additional","affiliation":[{"name":"Department of Hematology and Immunology Kagoshima University Hospital Japan"},{"name":"Division of Hematology and Immunology School of Medical and Dental Sciences Center for Chronic Viral Diseases Graduate Kagoshima University Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayako","family":"Kuroki","sequence":"additional","affiliation":[{"name":"Division of Hematology and Immunology School of Medical and Dental Sciences Center for Chronic Viral Diseases Graduate Kagoshima University Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Hirata","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology Kumamoto University Hospital Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Faculty of Sports and Health Science Fukuoka University Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Imakyure","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Care and Health Sciences Faculty of Pharmaceutical Sciences Fukuoka University Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanako","family":"Tone","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Faculty of Pharmaceutical Sciences Fukuoka University Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin\u2010ichiro","family":"Honda","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Faculty of Pharmaceutical Sciences Fukuoka University Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Soeda","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Faculty of Pharmaceutical Sciences Fukuoka University Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,4,13]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.15.1.15"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(07)70081-6"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.19.1.475"},{"issue":"1","key":"e_1_2_8_5_1","first-page":"S50","article-title":"Recent studies on the epidemiology, clinical features and pathogenic mechanisms of HTLV\u2010I associated myelopathy (HAM\/TSP) and other diseases associated to HTLV","volume":"3","author":"Osame M","year":"1997","journal-title":"J Neurovirol"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/101754"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.11.9958"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2001.02737.x"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-38965-8_12"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)70202-5"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2009.09.006"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.18.2428"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2111"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2011.08055.x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules191220295"},{"key":"e_1_2_8_16_1","first-page":"3625","article-title":"Clinical significance of CCR4 expression in adult T\u2010cell leukemia\/lymphoma: its close association with skin involvement and unfavorable outcome","volume":"9","author":"Ishida T","year":"2003","journal-title":"Clin Cancer Res"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.37.3472"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1468"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/1758-2946-5-30"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.9224"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1159\/000355328"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/483656"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000123072.34629.57"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules19032862"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm_00000046"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1991.tb08051.x"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.8.5718"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2008.272"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2003.11.008"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/294770a0"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.27481"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep11345"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.23860"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.21028"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2013.264"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.22536"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60327-409-8_9"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5381.1309"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.02.049"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1263"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI26390"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-11-0047"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2952"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-0572"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2401742"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2010.537"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-06-2567"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2007.09.003"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3415"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2008.150"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(04)00099-1"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2013.552"}],"container-title":["FEBS Open Bio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2F2211-5463.12055","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/2211-5463.12055","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/2211-5463.12055","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/2211-5463.12055","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,17]],"date-time":"2023-09-17T04:14:52Z","timestamp":1694924092000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1002\/2211-5463.12055"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,4,13]]},"references-count":51,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2016,5]]}},"alternative-id":["10.1002\/2211-5463.12055"],"URL":"https:\/\/doi.org\/10.1002\/2211-5463.12055","archive":["Portico"],"relation":{},"ISSN":["2211-5463","2211-5463"],"issn-type":[{"value":"2211-5463","type":"print"},{"value":"2211-5463","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,4,13]]},"assertion":[{"value":"2015-10-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-03-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-04-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}