Table 1.
Melatonin radiosensitizing effects as an antiangiogenic agent on endothelial cells.
| Changes in Angiogenesis related genes expression | Cytokines and angiogenic factors | ↓ Expression of CCL2 | Immunoregulatory and inflammatory processes |
| ↓ Expression of CXCL6 | Chemotactic and angiogenic properties |
||
| ↓ Expression of ERK1/2, AKT1 | Cell growth and differentiation |
||
| ↓ Expression of VEGFA, ANGPT2 | Angiogenesis and vascular development |
||
| Growth Factors and receptors | ↓ Expression of FGFR3, IGF-1 | Breast cancer: migration and proliferation | |
| ↓ Expression of JAG1 | Hematopoiesis and angiogenesis |
||
| ↓ Expression of TGFα | Cell proliferation and differentiation |
||
| ↓ Expression of KDR, ANPEP | Angiogenesis and vascular development |
||
| Proteases and extracellular matrix molecules | ↓ Expression of MMP14 | Cell growth, migration and tumor invasion | |
| ↑ Expression of TIMP1 | Degradation extracellular matrix and suppress proliferation |
||
| Modulation of estrogen biosynthesis | Decrease aromatase, sulfatase and 17β-HSD1 expression and activity | ||
| Inhibition of COX1/COX2 enzymes | |||
| Modulation of different steps of the angiogenic process | Decrease vascular area (CAM assay) | ||
| Inhibition of the activation of p-AKT and p-ERK | |||
| ↓ Permeability and VE-cadherin internalization | |||
| Inhibition of cell proliferation, migration, and tubular network | |||
CCL2, chemokine (C-C motif) ligand 2; CXCL6, chemokine (C-X-C motif) ligand 6 (granulocyte chemotactic protein 2); ERK, extracellular signal-regulated kinases; AKT1, V-akt murine thymoma viral oncogene homolog 1; VEGFA, vascular endothelial growth factor A; ANGPT2, angiopoietin 2; FGFR3, fibroblast growth factor receptor 3; IGF-1, insulin-like growth factor 1 (somatomedin C); JAG1, jagged canonical Notch ligand 1; TGFα, transforming growth factor, alpha; KDR, kinase insert domain receptor (a type III receptor tyrosine kinase); ANPEP, Alanyl (membrane) aminopeptidase; MMP14, matrix metallopeptidase 14 (membrane-inserted); TIMP1, TIMP metallopeptidase inhibitor 1; 17β-HSD1, 17β hydroxysteroid dehydrogenase type 1; COX1/COX2, cyclooxygenases type 1, 2; CAM, Chick Chorioallantoic Membrane.