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Guzey, M; Kitada, S; Reed, JC
<?xml version='1.0' encoding='utf-8'?> <oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd"> <dc:creator>Guzey, M</dc:creator> <dc:creator>Kitada, S</dc:creator> <dc:creator>Reed, JC</dc:creator> <dc:date>2002-01-01</dc:date> <dc:description>Calcitriol [1alpha,25-dihydroxyvitamin D-3] is the natural ligand of the vitamin D receptor (VDR). Using cultured prostate cancer (PC) cell lines, LN-CaP and ALVA-31, we studied the effects of 1alpha,25(OH)(2)-Vitamin D-3 (VD3) on expression of several apoptosis-regulating proteins including: (a) Bcl-2 family proteins (Bcl-2, Bcl-X-L, Mcl-1 Bax, and Bak); (b) the heat shock protein 70-binding protein BAG1L; and (c) IAP family proteins (XIAP, cIAP1, and cIAP2). VD3 induced decreases in levels of antiapoptotic proteins Bcl-2, Bcl-X-L, and Mcl-1, BAG1L, XIAP, cIAP1, and cIAP2 (without altering proapoptotic Bax and Bak) in association with increases in apoptosis. In contrast to VDR-expressing LN-CaP and ALVA-31 cells, VDR-deficient prostate cancer line Du-145 demonstrated no changes in apoptosis protein expression after treatment with VD3. In sensitive PC cell lines, VD3 activates downstream effector protease, caspase-3, and upstream initiator protease caspase-9, the apical protease in the mitochondrial ("intrinsic") pathway for apoptosis, but not caspase-8, an initiator caspase linked to an alternative ("extrinsic") apoptosis pathway triggered by cytokine receptors. VD3 induced declines in antiapoptotic proteins and also stimulated cytochrome c release from mitochondria by a caspase-independent mechanism. Moreover, apoptosis induction by VD3 was suppressed by over-expressing Bcl-2, a known blocker of cytochrome c release, whereas the caspase-8 suppressor CrmA afforded little protection. Thus, VD3 is capable of inhibiting expression of multiple antiapoptotic proteins in VDR-expressing prostate cancer cells, leading to activation of the mitochondrial pathway for apoptosis.</dc:description> <dc:identifier>https://aperta.ulakbim.gov.trrecord/96283</dc:identifier> <dc:identifier>oai:zenodo.org:96283</dc:identifier> <dc:rights>info:eu-repo/semantics/openAccess</dc:rights> <dc:rights>http://www.opendefinition.org/licenses/cc-by</dc:rights> <dc:source>MOLECULAR CANCER THERAPEUTICS 1(9) 667-677</dc:source> <dc:title>Apoptosis induction by 1 alpha,25-dihydroxyvitamin D-3 in prostate cancer</dc:title> <dc:type>info:eu-repo/semantics/article</dc:type> <dc:type>publication-article</dc:type> </oai_dc:dc>
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