1α,25-dihydroxyvitamin D3 and its TX527 analog inhibit the growth of endothelial cells transformed by Kaposi sarcoma-associated herpes virus G protein-coupled receptor in vitro and...

Authors
González Pardo, María Verónica; Martin, Daniel; Gutkind, J. Silvio; Verstuyf, Annemieke; Bouillon, Roger; Russo, Ana Josefa; Boland, Ricardo Leopoldo
Publication Year
2010
Language
English
Format
article
Status
Published version
Description
The Kaposi sarcoma-associated herpes virus-G protein-coupled receptor is a key molecule in the pathogenesis of Kaposi sarcoma, playing a central role in promoting vascular endothelial growth factor-driven angiogenesis and spindle cell proliferation. We studied the effects of 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] and the analog TX527 on the proliferation of endothelial cells (SVECs) and SVECs transformed by the viral G protein-coupled receptor (SVEC-vGPCR). 1α,25(OH)2D 3 and TX527 decreased SVEC-vGPCR and SVEC numbers, the response being time dependent and similar in both cell lines. Vitamin D receptor (VDR) levels increased on treatment with 10 nM 1α,25(OH)2D3 or 1 nM TX527 in a time-dependent manner (1.5-24 h) in SVECs and SVEC-vGPCR. Basal VDR levels were increased in SVEC-vGPCR. The antiproliferative effects were accompanied by reduction in cyclin D1 and accumulation of p27 in SVECs but not SVEC-vGPCR. Induction of VDR was blocked by transfection of short hairpinRNAagainst VDR in SVEC-vGPCR and the antiproliferative effects of 1α,25(OH)2D3 and TX527 were decreased, involving the VDR genomic pathway in the hormone and analog mechanism of action. In vivo experiments showed that 1α,25(OH)2D3 and TX527 decreased SVEC-vGPCR tumor progression when the tumor cells were implanted in nude mice. In conclusion, we have demonstrated that 1α,25(OH) 2D3 and its TX527 analog have antiproliferative effects on the growth of endothelial cells transformed by the vGPCR in vitro and in vivo, the vitamin D receptor being part of the inhibitory mechanism of action. Copyright © 2010 by The Endocrine Society.
Fil: González Pardo, María Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca; Argentina. Universidad Nacional del Sur; Argentina
Fil: Martin, Daniel. National Institutes of Health; Estados Unidos
Fil: Gutkind, J. Silvio. National Institutes of Health; Estados Unidos
Fil: Verstuyf, Annemieke. Katholieke Universiteit Leuven; Bélgica
Fil: Bouillon, Roger. Katholieke Universiteit Leuven; Bélgica
Fil: Russo, Ana Josefa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca; Argentina. Universidad Nacional del Sur; Argentina
Fil: Boland, Ricardo Leopoldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca; Argentina. Universidad Nacional del Sur; Argentina
Subject
1a, 25(OH)2 D3
TX527 ANALOG
VDR
CELL PROLIFERATION
Otras Ciencias Biológicas
Ciencias Biológicas
CIENCIAS NATURALES Y EXACTAS
Access level
Open access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/61766