PURPOSE: Eupatilin is an antioxidative flavone and a phytopharmaceutical derived 
from Artemisia asiatica. It has been reported to possess anti-tumor activity in 
some types of cancer including gastric cancer. Eupatilin may modulate the 
angiogenesis pathway which is part of anti-inflammatory effect demonstrated in 
gastric mucosal injury models. Here we investigated the anti-tumor effects of 
eupatilin on gastric cancer cells and elucidated the potential underlying 
mechanism whereby eupatilin suppresses angiogenesis and tumor growth.
MATERIALS AND METHODS: The impact of eupatilin on the expression of angiogenesis 
pathway proteins was assessed using western blots in MKN45 cells. Using a 
chromatin immunoprecipitation assay, we tested whether eupatilin affects the 
recruitment of signal transducer and activator of transcription 3 (STAT3), aryl 
hydrocarbon receptor nuclear translocator (ARNT) and hypoxia-inducible factor-1α 
(HIF-1α) to the human VEGF promoter. To investigate the effect of eupatilin on 
vasculogenesis, tube formation assays were conducted using human umbilical vein 
endothelial cells (HUVECs). The effect of eupatilin on tumor suppression in 
mouse xenografts was assessed.
RESULTS: Eupatilin significantly reduced VEGF, ARNT and STAT3 expression 
prominently under hypoxic conditions. The recruitment of STAT3, ARNT and HIF-1α 
to the VEGF promoter was inhibited by eupatilin treatment. HUVECs produced much 
foreshortened and severely broken tubes with eupatilin treatment. In addition, 
eupatilin effectively reduced tumor growth in a mouse xenograft model.
CONCLUSIONS: Our results indicate that eupatilin inhibits angiogenesis in 
gastric cancer cells by blocking STAT3 and VEGF expression, suggesting its 
therapeutic potential in the treatment of gastric cancer.