Angiogenesis is an essential process involved in various physiological, including placentation, and pathological, including
cancer and
endometriosis, processes.
Melatonin (MLT), a well‑known natural
hormone secreted primarily in the pineal gland, is involved in regulating neoangiogenesis and inhibiting the development of a variety of
cancer types, including lung and
breast cancer. However, the specific mechanism of its anti‑angiogenesis activity has not been systematically elucidated. In the present study, the effect of MLT on viability and angiogenesis of human umbilical vein endothelial cells (HUVECs), and the production of
vascular endothelial growth factor (
VEGF) and
reactive oxygen species (ROS), under normoxia or
hypoxia was analyzed using Cell Counting kit 8, tube formation, flow cytometry, ELISA and western blot assays. It was determined that the secretion of
VEGF by HUVECs was significantly increased under
hypoxia, while MLT selectively obstructed
VEGF release as well as the production of ROS under
hypoxia. Furthermore, MLT inhibited the viability of HUVECs in a dose‑dependent manner and reversed the increase in cell viability and tube formation that was induced by
hypoxia/
VEGF/H2O2. Additionally, treatment with an inhibitor of
hypoxia inducible factor (HIF)‑1α (KC7F2) and MLT synergistically reduced the release of ROS and
VEGF, and inhibited cell viability and tube formation of HUVECs. These observations demonstrate that MLT may serve dual roles in the inhibition of angiogenesis, as an
antioxidant and a
free radical scavenging agent. MLT suppresses the viability and angiogenesis of HUVECs through the downregulation of HIF‑1α/ROS/
VEGF. In summary, the present data indicate that MLT may be a potential
anticancer agent in solid
tumors with abundant blood vessels, particularly combined with KC7F2.