Extracts of the whole herb of Artemisia asiatica Nakai (Asteraceae) are used in
traditional oriental medicine to treat
inflammation.
Eupatilin (5,7-dihydroxy-3',4',6-trimethoxyflavone) is one of the pharmacologically active components found in A. asiatica, and has been shown to possess anti-tumoral effects in some
malignancies, including
gastric cancer. However, its anti-metastatic effect in
gastric cancer is hardly known. In this study, anti-metastatic effect of
eupatilin was investigated in the human
gastric cancer cell line, MKN-1.
Eupatilin inhibited MKN-1 growth in a dose- and a time-dependent manner, and induced apoptosis with a concomitant increase of
caspase-3 activity. ELISA demonstrated that release of pro-inflammatory
cytokines (IL-1β, TNF-α, IL-6, and IL-8) was significantly reduced by
eupatilin. And p-AKT and p-ERK (p44/42) was reduced. Expression level of β-
catenin and
integrin was reduced and p-GSKβ was increased. In transcription reporter system, the activity of the transcriptional factor, NF-κB, was reduced by
eupatilin and the expression of p65 was down-regulated when MKN-1 cells were treated with
eupatilin. Moreover, a zymography study revealed that this reduction in invasive potential resulted from a reduction in type IV collagenolytic (gelatinolytic) activity. The expressions of
metalloproteinases (MMP-2 and MMP-9) were also reduced in MKN-1 cells treated with
eupatilin. In vitro invasion assay,
eupatilin inhibited MKN-1 penetrating reconstituted basement membrane barriers. These results suggest that
eupatilin inhibits the MKN-1
gastric cancer cell proliferation via activation of
caspase-3 and the metastatic potential of
gastric cancer cells via down-regulation of NF-κB activity followed by reduction of pro-inflammatory
cytokine-mediated
MMPs expressions.