Abstract
Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, has been demonstrated to possess a strong antiangiogenic activity. However, the molecular mechanisms underlying this effect remain unclear. Endothelial cell (EC) migration is an essential component of angiogenesis, and the p38 mitogen-activated protein kinase (MAPK) signaling pathway plays a key role in the regulation of migration induced by vascular endothelial growth factor (VEGF). The aim of the present study was to investigate the effects of DHA on EC migration and the p38 MAPK signaling pathway. Human umbilical vein ECs (HUVECs) were treated with DHA and VEGF-induced migration was analyzed. The activation of p38 MAPK was detected by western blot analysis, and the migration assays were performed with a p38-specific inhibitor, SB203850. It was revealed that 20 μM DHA significantly reduced EC migration in the transwell migration assay, wound healing assay and electrical cell-substrate impedance sensing real-time analysis. However, DHA did not affect p38 MAPK phosphorylation or expression. In the absence or presence of SB203850, DHA induced a similar proportional reduction of EC migration in the three migration assays. Therefore, the present study demonstrated that DHA inhibits VEGF-induced EC migration via a p38 MAPK-independent pathway.
Highlights
Artemisinin is a sesquiterpene lactone isolated from the Artemisia annua plant that has been used extensively as an antimalarial drug [1]
Wound healing migration assays were performed, and the migrated area of Human umbilical vein endothelial cells (ECs) (HUVECs) was significantly reduced in the DHA‐treated groups when compared with the groups treated with vehicle dimethyl sulfoxide (DMSO) alone (40.97%, P
DHA‐induced repression of EC migration is unaffected by SB203850
Summary
Artemisinin is a sesquiterpene lactone isolated from the Artemisia annua plant that has been used extensively as an antimalarial drug [1]. DHA is an effective, water‐soluble antimalarial drug, with fewer side‐effects compared with other drugs [3]. DHA exhibits strong antitumor and antiangiogenesis effects [4]. Tumor cells or other growing cells secrete growth factors, including vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). These growth factors activate endothelial cells (ECs) in nearby capillaries, leading to the migration of ECs branching out of the vessel [7]. The cells proliferate and differentiate to form a network of new capillaries. It has been well established that solid tumor growth requires a neovascular network, which enables rapid proliferation of tumor cells by providing oxygen and nutrients [8]
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