Cell cycle arrest and apoptosis induced by 1,25(OH)2D3 and TX 527 in Kaposi sarcoma is VDR dependent
| Autor: | Ricardo Boland, Verónica González-Pardo, Annemieke Verstuyf, Ana Russo de Boland, Alejandra Suares, Pierre J. De Clercq |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
Cell cycle checkpoint Endocrinology Diabetes and Metabolism Otras Ciencias Biológicas Clinical Biochemistry Apoptosis Biology KAPOSI SARCOMA Biochemistry Calcitriol receptor Ciencias Biológicas Endocrinology Calcitriol Annexin Internal medicine medicine Animals Humans Receptor CELL CYCLE Sarcoma Kaposi Molecular Biology S phase Cholecalciferol Bone Density Conservation Agents Cell Cycle Checkpoints Cell Biology Cell cycle Molecular biology Gene Expression Regulation Neoplastic VITAMIN D Mechanism of action Alkynes Receptors Calcitriol Molecular Medicine medicine.symptom CIENCIAS NATURALES Y EXACTAS |
| Popis: | We have previously shown that 1α,25(OH)2-Vitamin D3 [1α,25(OH)2D3] and its less calcemic analog TX 527 inhibit the proliferation of endothelial cells transformed by the viral G protein-coupled receptor associated to Kaposi sarcoma (vGPCR) and this could be partially explained by the inhibition of the NF-κB pathway. In this work, we further explored the mechanism of action of both vitamin D compounds in Kaposi sarcoma. We investigated whether the cell cycle arrest and subsequent apoptosis of endothelial cells (SVEC) and SVEC transformed by vGPCR (SVEC-vGPCR) elicited by 1α,25(OH)2D3 and TX 527 were mediated by the vitamin D receptor (VDR). Cell cycle analysis of SVEC and SVEC-vGPCR treated with 1α,25(OH)2D3 (10 nM, 48 h) revealed that 1α,25(OH)2D3 increased the percentage of cells in the G0/G1 phase and diminished the percentage of cells in the S phase of the cell cycle. Moreover, the number of cells in the S phase was higher in SVEC-vGPCR than in SVEC due to vGPCR expression. TX 527 exerted similar effects on growth arrest in SVEC-vGPCR cells. The cell cycle changes were suppressed when the expression of the VDR was blocked by a stable transfection of shRNA against VDR. Annexin V-PI staining demonstrated apoptosis in both SVEC and SVEC-vGPCR after 1α,25(OH)2D3 and TX 527 treatment (10 nM, 24 h). Cleavage of caspase-3 detected by Western blot analysis was increased to a greater extent in SVEC than in SVEC-vGPCR cells, and this effect was also blocked in VDR knockdown cells. Altogether, these results suggest that 1α,25(OH)2D3 and TX 527 inhibit the proliferation of SVEC and SVEC-vGPCR and induce apoptosis by a mechanism that involves the VDR. Fil: González Pardo, María Verónica. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Suares, Alejandra Carolina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Verstuyf, Annemieke. Katholikie Universiteit Leuven; Bélgica Fil: De Clercq, Pierre. University of Ghent; Bélgica Fil: Boland, Ricardo Leopoldo. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Russo, Ana Josefa. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina |
| Databáze: | OpenAIRE |
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