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

  • Authors:
    • Alicia González-González
    • Alicia González
    • Carolina Alonso-González
    • Javier Menéndez-Menéndez
    • Carlos Martínez-Campa
    • Samuel Cos
  • View Affiliations

  • Published online on: November 2, 2017     https://doi.org/10.3892/or.2017.6070
  • Pages:433-441
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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.

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January 2018
Volume 39 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

2016 Impact Factor: 2.662
Ranked #31/217 Oncology
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APA
González-González, A., González, A., Alonso-González, C., Menéndez-Menéndez, J., Martínez-Campa, C., & Cos, S. (2018). Complementary actions of melatonin on angiogenic factors, the angiopoietin/Tie2 axis and VEGF, in co‑cultures of human endothelial and breast cancer cells. Oncology Reports, 39, 433-441. https://doi.org/10.3892/or.2017.6070
MLA
González-González, A., González, A., Alonso-González, C., Menéndez-Menéndez, J., Martínez-Campa, C., Cos, S."Complementary actions of melatonin on angiogenic factors, the angiopoietin/Tie2 axis and VEGF, in co‑cultures of human endothelial and breast cancer cells". Oncology Reports 39.1 (2018): 433-441.
Chicago
González-González, A., González, A., Alonso-González, C., Menéndez-Menéndez, J., Martínez-Campa, C., Cos, S."Complementary actions of melatonin on angiogenic factors, the angiopoietin/Tie2 axis and VEGF, in co‑cultures of human endothelial and breast cancer cells". Oncology Reports 39, no. 1 (2018): 433-441. https://doi.org/10.3892/or.2017.6070