INVESTIGADORES
CURINO Alejandro Carlos
congresos y reuniones científicas
Título:
The calcitriol analog EM1 exerts antineoplastic effects associated with VDR, p21 and p27 up-regulation.
Autor/es:
SALOMÓN, D.G.; BUSCHIAZZO, M.; VITALE, C.; MASCARÓ, E.; RADIVOY, G.; FALL, Y.; CURINO, A.C.; FACCHINETTI, M.M.
Lugar:
Los Cocos
Reunión:
Congreso; The First South American Spring Symposium in Signal Transduction and Molecular Medicine; 2010
Resumen:
The potent growth-inhibitory effects of calcitriol in several cell types make it an ideal compound to treat hyperproliferative disorders such as cancer. However, its hypercalcemic effects have severely hampered its therapeutic application and, to overcome this problem, structural analogs have been designed. In this work we analyzed the antineoplastic effects of the new phosphonate analog EM1 on several human and murine tumor cell lines. We found a significant decrease in cell survival in glioma cells, an effect greater than that elicited by calcitriol. The reduction in cellular survival was accompanied by an increase in VDR, p21waf1/cip1 and p27kip1 and a decrease in cyclin D1, while p53 protein levels were not affected. These results were confirmed by qPCR. Moreover, EM1 induced p21 levels in glioma whereas calcitriol decreased it. Similarly, in a Kaposi sarcoma cell model (SVEC vGPCR), EM1 exerted antiproliferative effects accompanied by VDR and p27 up regulation whereas the non-malignant cells (SVEC) did not respond to it. Importantly, EM1 showed complete lack of calcemic activity in mice. These results suggest that EM1 is a promising analogue showing antiproliferative effects in glioma and Kaposi sarcoma associated with up-regulation of VDR and the cell cycle inhibitors p21 and p27.