Inhibitory effects of eupatilin on tumor invasion of human gastric cancer MKN-1 cells
- Authors
- Park, Byeong Bae; Yoon, Jin Sun; Kim, Eun Shil; Choi, Jiyoung; Won, Young Woong; Choi, Jung Hye; Lee, Young Yiul
- Issue Date
- Apr-2013
- Publisher
- SAGE PUBLICATIONS LTD
- Keywords
- Growth inhibition; Gastric cancer; Eupatilin; Metastasis; Invasion
- Citation
- TUMOR BIOLOGY, v.34, no.2, pp.875 - 885
- Indexed
- SCIE
SCOPUS
- Journal Title
- TUMOR BIOLOGY
- Volume
- 34
- Number
- 2
- Start Page
- 875
- End Page
- 885
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/163132
- DOI
- 10.1007/s13277-012-0621-y
- ISSN
- 1010-4283
- Abstract
- 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-1 beta, TNF-alpha, IL-6, and IL-8) was significantly reduced by eupatilin. And p-AKT and p-ERK (p44/42) was reduced. Expression level of beta-catenin and integrin was reduced and p-GSK beta was increased. In transcription reporter system, the activity of the transcriptional factor, NF-kappa B, 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-kappa B activity followed by reduction of pro-inflammatory cytokine-mediated MMPs expressions.
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