1 Ocak 2002 Dergi makalesi Açık Erişim

Guzey, M; Kitada, S; Reed, JC

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{
  "URL": "https://aperta.ulakbim.gov.tr/record/96283", 
  "abstract": "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.", 
  "author": [
    {
      "family": "Guzey", 
      "given": " M"
    }, 
    {
      "family": "Kitada", 
      "given": " S"
    }, 
    {
      "family": "Reed", 
      "given": " JC"
    }
  ], 
  "container_title": "MOLECULAR CANCER THERAPEUTICS", 
  "id": "96283", 
  "issue": "9", 
  "issued": {
    "date-parts": [
      [
        2002, 
        1, 
        1
      ]
    ]
  }, 
  "page": "667-677", 
  "title": "Apoptosis induction by 1 alpha,25-dihydroxyvitamin D-3 in prostate cancer", 
  "type": "article-journal", 
  "volume": "1"
}