Antineoplastic mechanism of Vitamin D in endothelial tumor cells

VERONICA GONZALEZ PARDO; CINTHYA TAPIA; ALEJANDRA SUARES

Buenos Aires

Congreso; Buenos Aires research conferences on autophagy. Molecular mechanisms in biology and diseases; 2017

ICGEB

The hormonally active form of vitamin D3, 1α,25-dihydroxyvitamin D3, and its less calcemic analogue, TX 527, are novel anticancer agents participating in growth inhibition, differentiation, and apoptosis in tumor cells. We have previously shown that VDR agonists induced cell cycle arrest and apoptosis in endothelial cells transformed by Kaposi?s sarcoma-associated Herpes virus G Protein-Coupled Receptor (vGPCR). In this work, we studied ERK 1/2, Akt, BAD and MKP-3 role in the antiproliferative actions of VDR agonists. Time (12-48 h) and dose response (0.1-100 nM) western blot studies showed a decrease of p-Akt and p-ERK1/2, in counteract with p-BAD rise and MKP-3 protein accumulation. Beclin-1 has a central role in autophagy, which is increased during periods of cell stress. qRT-PCR time response studies (0.3-48 h) exhibited an early increased on Beclin-1 gene expression between 0.3-1 h, and a later one at 48 h. Taken together, these results suggest that VDR agonists regulate signaling pathways that in turn induce apoptosis and trigger autophagy which could control first a survival path and later an apoptotic one.