Eupatilin inhibits angiogenesis-mediated human hepatocellular metastasis by reducing MMP-2 and VEGF signaling

Authors
Park, Jun YeonPark, Do HwiJeon, YoungsicKim, Young-JooLee, JaeminShin, Myoung-SookKang, Ki SungHwang, Gwi SeoKim, Hyun YoungYamabe, Noriko
Issue Date
2018-10-15
Publisher
Pergamon Press Ltd.
Citation
Bioorganic & Medicinal Chemistry Letters, v.28, no.19, pp.3150 - 3154
Abstract
Metastasis is responsible for the great majority of deaths in cancer patients. Matrix metalloproteinases (MMPs) have critical functions in cancer metastasis. Especially, MMP-2 and MMP-9 play a major role in tumor-cell migration and invasion. Therefore, to first find out the inhibitory effect of eupatilin on expression of MMPs in SNU182 cells, we used quantitative real-rime PCR to measure MMP-2 and MMP-9 mRNA levels. Eupatilin suppressed transcription of MMP-2 in SNU182 cells more than did the corresponding controls. Also, eupatilin significantly blocked tube formation when treated with a concentration of 3.125 or 6.25 mu g/mL on human umbilical vein vascular endothelial cells (HUVECs). Eupatilin induced significant anti-angiogenic potential associated with down-regulation of hypoxia-inducible factor 1-alpha (HIF-1 alpha), vascular endothelial growth factor (VEGF), and phosphorylated Akt expression. Thus, tube-formation inhibition and MMP-2-mediated migration are likely to be important therapeutic targets of eupatilin in hepatocellular carcinoma metastasis.
Keywords
NITRIC-OXIDE SYNTHASE; MATRIX METALLOPROTEINASES; EXPRESSION; CARCINOMA; PATHOGENESIS; COLLAGENASE; MIGRATION; EXTRACT; CELLS; ACID; NITRIC-OXIDE SYNTHASE; MATRIX METALLOPROTEINASES; EXPRESSION; CARCINOMA; PATHOGENESIS; COLLAGENASE; MIGRATION; EXTRACT; CELLS; ACID; Eupatilin; Metastasis; HUVEC; MMPs; VEGF
ISSN
0960-894X
URI
https://pubs.kist.re.kr/handle/201004/120784
DOI
10.1016/j.bmcl.2018.08.034
Appears in Collections:
KIST Article > 2018
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