TY - JOUR AB - 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. AD - Laboratory for Reproductive Immunology, Key Laboratory of Reproduction Regulation of NPFPC, SIPPR, IRD, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai 200011, P.R. China Center for Human Reproduction and Genetics, Suzhou Municipal Hospital, Suzhou, Jiangsu 215008, P.R. China Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China Department of Gynecology, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai 200011, P.R. China AU - Cheng,Jiao AU - Yang,Hui‑Li AU - Gu,Chun‑Jie AU - Liu,Yu‑Kai AU - Shao,Jun AU - Zhu,Rui AU - He,Yin‑Yan AU - Zhu,Xiao‑Yong AU - Li,Ming‑Qing DA - 2019/02/01 DO - 10.3892/ijmm.2018.4021 EP - 955 IS - 2 JO - Int J Mol Med KW - melatonin hypoxia vascular endothelial growth factor reactive oxygen species angiogenesis PY - 2019 SN - 1107-3756 1791-244X SP - 945 ST - Melatonin restricts the viability and angiogenesis of vascular endothelial cells by suppressing HIF-1α/ROS/VEGF T2 - International Journal of Molecular Medicine TI - Melatonin restricts the viability and angiogenesis of vascular endothelial cells by suppressing HIF-1α/ROS/VEGF UR - https://doi.org/10.3892/ijmm.2018.4021 VL - 43 ER -