Berberine Inhibits Endothelial Cell Proliferation via Repressing ERK1/2 Pathway

Abstract

Abnormal angiogenesis plays a key role in cancer progression. In recent years, anti-angiogenic therapy has attracted increasing attention. Berberine (BBR), the main component extracted from Coptis (Ranunculaceae) rhizome, has an anti-angiogenic effect. However, the underlying mechanisms remain to be elucidated. Endothelial cell proliferation is a pivotal process in angiogenesis. In our research, we observed that BBR specifically downregulated the expression of the extracellular signal-regulated kinase 1/2 (ERK1/2) protein in human umbilical vein endothelial cells (HUVECs). The role of BBR in HUVEC proliferation was then assessed using methylthiazolyldiphenyl-tetrazolium bromide and cell counting Kit-8 (CCK-8) assays. The effect of BBR on the ERK1/2 signaling pathway was evaluated using Western blotting. BBR decreased HUVEC proliferation in a dose-dependent manner and inhibited the expression of phospho-ERK1/2 in HUVECs. PD98059, a specific inhibitor of ERK1/2 signaling, attenuated the BBR-induced decrease in the proliferation of HUVECs. Phorbol 12-myristate 13-acetate, a natural activator of ERK1/2 signaling, did not alter BBR-induced proliferation. In conclusion, BBR inhibited endothelial cell proliferation by suppressing ERK1/2 signaling. These findings may provide a potential therapeutic strategy for suppressing tumor growth.