{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T06:34:52Z","timestamp":1791095692068,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2008,9,16]],"date-time":"2008-09-16T00:00:00Z","timestamp":1221523200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2008,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Adult T\u2010cell leukemia (ATL) is a fatal malignancy of T lymphocytes caused by human T\u2010cell leukemia virus type 1 (HTLV\u20101) infection and remains incurable. Carotenoids are a family of natural pigments and have several biological functions. Among carotenoids, fucoxanthin is known to have antitumorigenic activity, but the precise mechanism of action is not elucidated. We evaluated the anti\u2010ATL effects of fucoxanthin and its metabolite, fucoxanthinol. Both carotenoids inhibited cell viability of HTLV\u20101\u2010infected T\u2010cell lines and ATL cells, and fucoxanthinol was approximately twice more potent than fucoxanthin. In contrast, other carotenoids, \u03b2\u2010carotene and astaxanthin, had mild inhibitory effects on HTLV\u20101\u2010infected T\u2010cell lines. Importantly, uninfected cell lines and normal peripheral blood mononuclear cells were resistant to fucoxanthin and fucoxanthinol. Both carotenoids induced cell cycle arrest during G\n                    <jats:sub>1<\/jats:sub>\n                    phase by reducing the expression of cyclin D1, cyclin D2, CDK4 and CDK6, and inducing the expression of GADD45\u03b1, and induced apoptosis by reducing the expression of Bcl\u20102, XIAP, cIAP2 and survivin. The induced apoptosis was associated with activation of caspase\u20103, \u20108 and \u20109. Fucoxanthin and fucoxanthinol also suppressed I\u03baB\u03b1 phosphorylation and JunD expression, resulting in inactivation of nuclear factor\u2010\u03baB and activator protein\u20101. Mice with severe combined immunodeficiency harboring tumors induced by inoculation of HTLV\u20101\u2010infected T cells responded to treatment with fucoxanthinol with suppression of tumor growth, showed extensive tissue distribution of fucoxanthinol, and the presence of therapeutically effective serum concentrations of fucoxanthinol. Our preclinical data suggest that fucoxanthin and fucoxanthinol could be potentially useful therapeutic agents for patients with ATL. \u00a9 2008 Wiley\u2010Liss, Inc.\n                  <\/jats:p>","DOI":"10.1002\/ijc.23860","type":"journal-article","created":{"date-parts":[[2008,9,16]],"date-time":"2008-09-16T16:05:15Z","timestamp":1221581115000},"page":"2702-2712","source":"Crossref","is-referenced-by-count":122,"title":["Antiadult T\u2010cell leukemia effects of brown algae fucoxanthin and its deacetylated product, fucoxanthinol"],"prefix":"10.1002","volume":"123","author":[{"given":"Chie","family":"Ishikawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senji","family":"Tafuku","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Kadekaru","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeki","family":"Sawada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariko","family":"Tomita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taeko","family":"Okudaira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuro","family":"Nakazato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayoshi","family":"Toda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun\u2010Nosuke","family":"Uchihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoya","family":"Taira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuiku","family":"Ohshiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Yasumoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takao","family":"Ohta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Mori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,9,16]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.77.12.7415"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.78.10.6476"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.79.6.2031"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2001.02737.x"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3835(97)04662-4"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/19.1.81"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2005.03.002"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/131.12.3303"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2004.08.012"},{"key":"e_1_2_6_11_2","first-page":"361","article-title":"Proton\u2010donative 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