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Complementary actions of melatonin on angiogenic factors, the angiopoietin/Tie2 axis and VEGF, in co-ultures of human endothelial and breast cancer cells

Abstract: Melatonin exerts oncostatic activity in breast cancer through antiangiogenic actions. There, the aim of the present study was to ascertain whether melatonin modulates, in a coordinated action, angiopoietin-1 (ANG-1), ANG-2, their cognate Tie2 receptor and VEGF in co-cultures of human endothelial cells (HUVECs) and breast cancer (MCF-7) cells. To accomplish this we used co-cultures of human breast cancer cells (MCF-7) or non-malignant human mammary epithelial cells (MCF?10A) with endothelial cells (HUVECs). The presence of breast cancer cells increased HUVEC proliferation and 1 mM melatonin prevented this effect. ANG-1, ANG-2 and VEGF levels in co-culture media and mRNA expression were upregulated and Tie2 mRNA expression was downregulated in the HUVECs and MCF-7. Melatonin (1 mM) downregulated ANG-1, ANG-2 and VEGF levels in the co-culture media and mRNA expression in both types of cells and upregulated Tie2 mRNA expression in HUVECs. ANG-1, ANG-2, Tie2 and VEGF mRNA expression were not modified during HUVEC/MCF-10A co-culture. Estradiol (10 nM) increased ANG-1, ANG-2 and VEGF mRNA expression in HUVECs and melatonin (1 mM) counteracted this effect. We conclude that melatonin simultaneously coordinates downregulation of angiopoietins with a reduction in VEGF, which could be an effective therapeutic strategy for blocking tumor angiogenesis.

 Fuente: Oncol Rep. 2018 Jan;39(1):433-441

Editorial: Spandidos Publications

 Fecha de publicación: 01/01/2018

Nº de páginas: 9

Tipo de publicación: Artículo de Revista

 DOI: 10.3892/or.2017.6070

ISSN: 1021-335X,1791-2431

Proyecto español: SAF2013-42012-P ; SAF2016-77103-P

Url de la publicación: https://dx.doi.org/10.3892/or.2017.6070