Trigonostemon reidioides modulates endothelial cell proliferation, migration and tube formation via downregulation of the Akt signaling pathway

Trigonostemon reidi`oides (TR) is used as a Thai traditional medicine for the treatment of drug addiction, asthma, food poisoning, constipation and snake bites. The present study investigated the effects and molecular mechanisms of the ethanolic extract of TR (ETR) on mitogen-induced human umbilical vein endothelial cells (HUVECs) responses, proliferation, adhesion, migration and tube formation. ETR treatment inhibited mitogen-induced HUVEC proliferation by downregulation of cell cycle-associated proteins, including cyclins and cyclin-dependent kinases, which induced retinoblastoma protein hypophosphorylation. The present study also demonstrated that ETR treatment suppressed mitogen-induced HUVEC adhesion, migration, invasion and tube formation, and that these anti-angiogenic activities were mediated by inactivation of mitogen-induced Akt and matrix metalloproteinase (MMP)-2, but not of extracellular signal-regulated kinase, p70 ribosomal S6 kinase or MMP-9. Collectively, the results of the present study suggested pharmacological functions and molecular mechanisms of ETR in regulating endothelial cell fates, and supported further evaluation and development of ETR as a potential therapeutic agent for the treatment and prevention of angiogenesis-associated diseases, including cancer.