Angiogenesis, coagulation, and fibrinolytic markers in acute promyelocytic leukemia (NB4): An evaluation of melatonin effects.

Melatonin is a powerful biological agent that has been shown to inhibit angiogenesis and also exert anti-inflammatory effects. It is well known that new blood vessel formation (angiogenesis) has become an urgent issue in leukemia as well as solid tumors. Acute promyelocytic leukemia (APL) is a form of liquid cancer that manifests increased angiogenesis in the bone marrow of patients. Despite high-rate curable treatment with all trans retinoic acid (ATRA) and recently arsenic trioxide (ATO), early death because of hemorrhage, coagulopathy, and Disseminated intravascular coagulation (DIC) remains still a concerning issue in these patients. It is therefore urgent to seek treatment strategies with antiangiogenic capabilities that also diminish coagulopathy and hyperfibrinolysis in APL patients. In this study, a co-culture system with human umbilical vein endothelial cells (HUVECs) and NB4 APL cells were used to investigate the direct effect of melatonin on angiogenesis and its possible action on tissue factor (TF) and tissue type plasminogen activator-1 (TPA-1) expression. Our experiments revealed that HUVEC-induced angiogenesis by co-cultured NB4 cells was suppressed when melatonin alone or in combination with ATRA was added to the incubation medium. Melatonin at concentrations of 1mM inhibited tube formation of HUVECs and also decreased interleukin-6 (IL-6) secretion and VEGF mRNA expression in HUVEC and NB4 cells. Taken together, the results of this study demonstrate that melatonin inhibits accelerated angiogenesis of HUVECs and ameliorates the coagulation and fibrinolysis indices stimulated by co-culturing with NB4 cells. This article is protected by copyright. All rights reserved.