Inhibition of vascular endothelial growth factor expression by Chinese medicine of Hedyotis diffusa Willd herbal compounds

Abstract

The Hedyotis diffusa Willd herbal compounds (HDWHCs) are commonly used as Chinese medicine to treat cancer patients with established clinical therapeutic efficacy in China. However, the underlying mechanisms remain to be elucidated. In this study, we used freeze-dried powder of the water extracts of HDWHCs to investigate the potential mechanisms of HDWHCs in cancer treatment. HDWHCs treatment significantly inhibited vascular endothelial growth factor (VEGF) mRNA levels and VEGF transcriptional activation in cancer cells. HDWHCs also had a remarkable inhibitory effect on the expression of hypoxia-inducible factor 1alpha (HIF-1alpha). Forced expression of HIF-1α restored VEGF transcriptional activation inhibited by HDWHCs, indicating that HDWHCs suppressed VEGF expression through decreasing HIF-1alpha expression. Moreover, HDWHCs inhibited cyclooxygenase-2 (COX-2) expression, and overexpression of HIF-1alpha restored HDWHCs’ inhibitory effect on COX-2 at transcriptional level. These findings may provide better understanding of HDWHCs’ anti-cancer mechanism in cancer treatment.

Keywords

Hedyotis diffusa Willd / Chinese medicine / vascular endothelial growth factor (VEGF) / hypoxia-inducible factor 1alpha (HIF-1alpha) / cyclooxygenase-2 (COX-2)