Down-regulation of COX-2 activity by 1α,25(OH)2D3 is VDR dependent in endothelial cells transformed by Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor

Autor: Maria del Carmen Fernandez, Juan Francisco Viso, Cinthya Tapia, Cecilia I. Casali, John H. White, Fernando Zamarreño, Verónica González-Pardo, Gabriela Alejandra Salvador
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Biocomputational method
TOXICOLOGY
Cancer research
1α
25(OH)2D3
Toxicology
medicine.disease_cause
Calcitriol receptor
Biochemistry
Ciencias Biológicas
purl.org/becyt/ford/1 [https]
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
medicine
CANCER RESEARCH
Viability assay
Kaposi's sarcoma-associated herpesvirus
lcsh:Social sciences (General)
Receptor
purl.org/becyt/ford/1.6 [https]
lcsh:Science (General)
Kaposi's sarcoma
G protein-coupled receptor
VDR
Multidisciplinary
Chemistry
KAPOSI'S SARCOMA
Bioquímica y Biología Molecular
COX-2
medicine.disease
ONCOLOGY
Molecular biology
1Α
25(OH)2D3
030104 developmental biology
Oncology
Apoptosis
BIOCOMPUTATIONAL METHOD
BIOCHEMISTRY
lcsh:H1-99
CIENCIAS NATURALES Y EXACTAS
030217 neurology & neurosurgery
Research Article
lcsh:Q1-390
Zdroj: Heliyon, Vol 6, Iss 10, Pp e05149-(2020)
CONICET Digital (CONICET)
Consejo Nacional de Investigaciones Científicas y Técnicas
instacron:CONICET
Heliyon
ISSN: 2405-8440
Popis: Our previous reports showed that 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) has antiproliferative actions in endothelial cells stably expressing viral G protein-coupled receptor (vGPCR) associated with the pathogenesis of Kaposi's sarcoma. It has been reported that COX-2 enzyme, involved in the tumorigenesis of many types of cancers, is induced by vGPCR. Therefore, we investigated whether COX-2 down-regulation is part of the growth inhibitory effects of 1α,25(OH)2D3. Proliferation was measured in presence of COX-2 inhibitor Celecoxib (10–20 μM) revealing a decreased in vGPCR cell number, displaying typically apoptotic features in a dose dependent manner similarly to 1α,25(OH)2D3. In addition, the reduced cell viability observed with 20 μM Celecoxib was enhanced in presence of 1α,25(OH)2D3. Remarkably, although COX-2 mRNA and protein levels were up-regulated after 1α,25(OH)2D3 treatment, COX-2 enzymatic activity was reduced in a VDR-dependent manner. Furthermore, an interaction between COX-2 and VDR was revealed through GST pull-down and computational analysis. Additionally, high-affinity prostanoid receptors (EP3 and EP4) were found down-regulated by 1α,25(OH)2D3. Altogether, these results suggest a down-regulation of COX-2 activity and of prostanoid receptors as part of the antineoplastic mechanism of 1α,25(OH)2D3 in endothelial cells transformed by vGPCR.
1α,25(OH)2D3; VDR; COX-2; Kaposi's sarcoma; Biocomputational method; Biochemistry; Cancer research; Toxicology; Oncology.
Databáze: OpenAIRE
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