{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T01:25:59Z","timestamp":1760318759698},"reference-count":33,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2008,3,6]],"date-time":"2008-03-06T00:00:00Z","timestamp":1204761600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2008,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Vitamin E analog, 2,5,7,8\u2010tetramethyl\u20102R\u2010(4R,8R, 12\u2010trimethyltridecyl) chroman\u20106\u2010yloxyacetic acid, referred to as \u03b1\u2010TEA induces apoptosis in a variety of human cancer cells in cell culture and reduces tumor burden and metastases in preclinical animal models of breast and ovarian cancer. The goal of this study was to determine in vivo anticancer efficacy of \u03b1\u2010TEA against human prostate cancer cells and identify mechanisms of action.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>A PC\u20103\u2010GFP xenograft model was used to assess the effects of \u03b1\u2010TEA formulated in liposomes and administered orally on tumor burden and metastases. Tumor tissue was examined by immunohistochemical staining for percentage of cells undergoing apoptosis by TUNEL or cell proliferation by Ki\u201067. In vitro analyses of mechanisms employed western immunoblotting to examine effects of \u03b1\u2010TEA\u2010treatments in LNCaP and PC\u20103\u2010GFP cells on levels of pro\u2010survival and pro\u2010death factors. Functional significance was determined using ectopically expressed constitutively active forms, inhibitors, or siRNA.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>\u03b1\u2010TEA significantly reduced tumor burden and metastases, increased apoptosis and decreased proliferation of tumor cells (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). \u03b1\u2010TEA treatment of both LNCaP and PC\u20103\u2010GFP cells in vitro reduced levels of pAkt1, pAkt2; FOXO1, c\u2010FLIP(L) and survivin. Constitutively active Akt1, Akt2, c\u2010FLIP or survivin reduced \u03b1\u2010TEA\u2010induced apoptosis. PI3K inhibitor enhanced apoptosis. Constitutively active FOXO1 enhanced \u03b1\u2010TEA induced Fas ligand expression; whereas, FOXO1 siRNA reduced \u03b1\u2010TEA induced Fas ligand expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>\u03b1\u2010TEA is an effective anticancer agent for human prostate cancer cells. Downregulation of pro\u2010survival and upregulation of pro\u2010death factors play roles in \u03b1\u2010TEA\u2010induced apoptosis. Prostate 68:849\u2013860, 2008. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.20750","type":"journal-article","created":{"date-parts":[[2008,3,6]],"date-time":"2008-03-06T17:28:36Z","timestamp":1204824516000},"page":"849-860","source":"Crossref","is-referenced-by-count":33,"title":["In vivo and in vitro studies of anticancer actions of \u03b1\u2010TEA for human prostate cancer cells"],"prefix":"10.1002","volume":"68","author":[{"given":"Li","family":"Jia","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiping","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bob 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