Comparative effects of 1,25(OH)2D3 and EB1089 on cell cycle kinetics and apoptosis in MCF-7 breast cancer cells

作者: Maura Simboli-Campbell , Carmen J. Narvaez , Kathryn VanWeelden , Martin Tenniswood , JoEllen Welsh

DOI: 10.1023/A:1005772432465

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摘要: 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the active metabolite of vitamin D, inhibits breast cancer cell growth both in vivo and vitro. In addition to its anti-proliferative effects, 1,25(OH)2D3 induces morphological biochemical markers apoptosis MCF-7 cells. studies reported here, we compared effects EB1089, a low calcemic D analog, on cycle kinetics Both compounds reduced viable number time dose dependent manner, with EB1089 approximately 50 fold more potent than 1,25(OH)2D3. Flow cytometric analysis indicated that agents induced arrest G0/G1 which was associated accumulation hypophosphorylated form retinoblastoma (Rb) protein. cells treated either or for 48 h exhibited characteristics apoptosis, including cytoplasmic condensation, pyknotic nuclei, condensed chromatin DNA fragmentation. Cells agent up regulation proteins mammary gland regression (clusterin cathepsin B) down anti-apoptotic protein bcl-2. These demonstrate that, despite lower activity vivo, analog are indistinguishable from those number, indices addition, since rapidly regulate estrogen receptor, disruption signalling may play role induction by

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