Abstract

Rg1 is a predominant protopanaxatriol-type of ginsenoside found in Panax ginseng, and it has been shown to have anti-cancer effects in multiple types of cancer cells. However, Rg1 also induces the expression of proangiogenic factors, such as vascular endothelial growth factor (VEGF-A), in endothelial cells. Unfortunately, angiogenesis positively correlates with cancer development. In this study, we identified RUNX2 as a regulator of ginsenoside Rg1-induced angiogenesis for the first time. We found that RUNX2 was directly targeted and regulated by miR-23a. Additionally, miR-23a was shown to inhibit angiogenesis in both human umbilical vein endothelial cells (HUVECs) and in zebrafish. Furthermore, a decrease in RUNX2 expression resulted in translational repression of VEGF-A in HUVECs. Taken together, this study identified a MiR-23a/RUNX2/VEGF-A pathway in angiogenesis and shed light on the molecular mechanism of Rg1-induced angiogenesis. Thus, RUNX2 might be a potential therapeutic target in Rg1-mediated angiogenesis in cancer.

Highlights

  • Traditional Chinese medicine has proven to be a promising route in the development of new drugs

  • We found that Rg1 increased RUNX2 expression in a dosedependent manner (Figure 1A)

  • Rg1 has an angiogenic function in endothelial cells, which may promote cancer development

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Summary

Introduction

Traditional Chinese medicine has proven to be a promising route in the development of new drugs. The most recent studies show that most of the biological activities of ginseng can be attributed to a group of triterpenoid saponins known as ginsenosides [35] According to their chemical structures, ginsenosides were classified into protopanaxadiol type (PPD-type) and protopanaxatriol type (PPT-type). Numerous studies demonstrate that Rg1 strongly induces proangiogenic factors, such as nitric oxide (NO) and VEGF-A in human umbilical vein endothelial cells (HUVECs). This induction functions through pathways dependent on phosphatidylinositol 3-kinase (PI3K)/Protein kinase B (Akt), b-catenin/T-cell factor, and hypoxia-inducible factor-1a (HIF-1a) [16, 17]. The function of Rg1 is different and relatively independent in cancer cells and endothelial cells, it has been establish that the angiogenic functions in endothelial cells can advance cancer development [18]

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