Teucrium polium Extract Enhances the Anti-Angiogenic Effect of Tranilast in a Three-Dimensional Fibrin Matrix Model

OBJECTIVE: Angiogenesis plays a dominant role in many pathophysiologic disorders, including cancer. Tranilast, which is an anti-fibrotic drug, is also suggested as an anti-angiogenesis agent. As Teucrium polium (TP) is known as an herbal medicine with antitumor properties, this study aimed to investigate the effects of TP and Tranilast on human umbilical vein endothelial cells (HUVECs), in vitro model of angiogenesis, as well as rat’s aortic ring ex vivo model. METHODS: In this study, The HUVECs were treated with various doses of TP and Tranilast each one alone or in combination together. Cell survival test, aortic ring ex-vivo assay, and evaluating mRNA expressions of VEGFA and TGF-β ligands and receptors were performed. RESULTS: The survival rate of HUVECs has significantly (p<0.05) reduced by TP and Tranilast. The combination of both TP and Tranilast significantly reduced cell viability as compared to the administration of TP or Tranilast alone. As well, the treatment of HUVECs with TP and/or Tranilast significantly (p<0.05) decreased TGF-β1, TGF-β 2, TGF-βRI, and TGF-βRII mRNA expression levels, but not the expression of TGF-β3 and TGF-βRIII in the TP-treated cells. Image analysis showed that TP and/or Tranilast inhibited vascular growth in the aortic ring assay. CONCLUSION: Our results strongly support the anti-angiogenic effects of the TP and Tranilast combination on both in vitro and ex vivo models of angiogenesis. However, further investigations in in vivo models and human studies are needed before human use.