Dihydroartemisinin inhibits angiogenesis in breast cancer via regulating VEGF and MMP‐2/‐9

Abstract

BackgroundDihydroartemisinin (DHA) is an artemisinin derivative known for its antimalarial properties. It has also shown potential as an anti‐tumor and anti‐angiogenic agent. However, its specific role in inhibiting angiogenesis in breast cancer is not well understood.ObjectivesWe aimed to investigate the anti‐angiogenesis effect of DHA on breast cancer and explore its potential as a therapeutic drug. Our objectives were to assess the impact of DHA on neovascularization induced by MDA‐MB‐231 cells, evaluate its effects on vessel sprout and tube‐formation in vascular endothelial cells, and analyze the expression of key angiogenesis‐related proteins.MethodsUsing a chicken chorioallantoic membrane (CAM) model, we cultured MDA‐MB‐231 cells and treated them with DHA. We assessed neovascularization and cultured vascular endothelial cells with DHA‐treated cell media to evaluate vessel sprout and tube‐formation. Protein expression levels of VEGF, MMP‐2, and MMP‐9 were analyzed using Western blotting.ResultsDHA significantly attenuated neovascularization induced by MDA‐MB‐231 cells. It also suppressed vessel sprout and tube‐formation of HUVEC cells when exposed to DHA‐treated cell media. Furthermore, DHA downregulated the expression of VEGF, MMP‐2, and MMP‐9 proteins. Mechanistically, DHA inhibited the phosphorylation of PI3K, AKT, ERK, and NF‐κB proteins in tumor cells.ConclusionsOur study provides evidence of the inhibitory effect of DHA on breast cancer angiogenesis. These findings support the potential of DHA as an anti‐breast cancer drug and warrant further investigation for its therapeutic applications.