Dual inhibition of angiogenesis by Peucedanum praeruptorum Dunn root extract in endothelial and gefitinib-resistant lung cancer cells.

Peucedanum praeruptorum Dunn (PP) root, traditionally used in Korea to alleviate respiratory symptoms, has been reported to exhibit anticancer effects. In this study, we investigated the effects of an ethanolic extract of PP root (EPP) on tumor angiogenesis. The anti-angiogenic activity of EPP was evaluated in both endothelial and cancer cells. Our results showed that EPP significantly inhibited the proliferation, migration, tube formation, and permeability of human umbilical vein endothelial cells (HUVECs), indicating that EPP suppresses the angiogenic capacity of HUVECs. EPP also reduced VEGFR2 phosphorylation and the activation of its downstream targets, AKT and ERK. Conditioned medium (CM) from gefitinib-resistant PC9 (PC9/GR) cells promoted HUVEC migration, tube formation, and angiogenic factor expression compared with CM from parental PC9 cells, demonstrating the strong pro-angiogenic properties of PC9/GR cells. Notably, CM from PC9/GR cells treated with EPP (EPP CM) markedly suppressed these pro-angiogenic effects. EPP selectively downregulated angiopoietin-1 (ANG-1) in PC9/GR cells, and supplementation with recombinant human ANG-1 to EPP CM restored HUVEC migration. Praeruptorin A (PA) and praeruptorin B (PB), constituents of EPP, exhibited comparable anti-angiogenic activities in both HUVECs and PC9/GR cells and were predicted to bind the VEGFR2 kinase domain. Taken together, these findings suggest that EPP inhibits angiogenesis through dual mechanisms: direct inactivation of VEGFR2 in endothelial cells and attenuation of the pro-angiogenic potential of PC9/GR cells via ANG-1 downregulation. This study highlights the therapeutic potential of EPP as a natural anti-angiogenic agent.