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

Abstract

BACKGROUND:

Dihydroartemisinin (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.

OBJECTIVES:

We 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.

METHODS:

Using 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.

RESULTS:

DHA 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.

CONCLUSIONS:

Our 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.

• Authors: Qi Rao, He Yu, Ruochan Li, Bin He, Yuxue Wang, Xiaohong Guo, Gang Zhao, Fenghua Wu
• Journal: Fundamental & clinical pharmacology (Fundam Clin Pharmacol) (Jul 25 2023) ISSN: 1472-8206 [Electronic] England
• PMID: 37490927 (Publication Type: Journal Article)
• Copyright: © 2023 Société Française de Pharmacologie et de Thérapeutique Published by John Wiley & Sons Ltd.