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Resveratrol analog‐3,5,4′‐trimethoxy‐ trans ‐stilbene inhibits invasion of human lung adenocarcinoma cells by suppressing the MAPK pathway and decreasing matrix metalloproteinase‐2 expression
Author(s) -
Yang YaTing,
Weng ChiaJui,
Ho ChiTang,
Yen GowChin
Publication year - 2009
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.200800123
Subject(s) - resveratrol , p38 mitogen activated protein kinases , a549 cell , chemistry , mapk/erk pathway , phosphorylation , kinase , signal transduction , protein kinase a , downregulation and upregulation , matrix metalloproteinase , microbiology and biotechnology , activator (genetics) , cell culture , cancer research , cell , biochemistry , biology , receptor , gene , genetics
Resveratrol (3,5,4′‐trihydroxystilbene) is a natural polyphenol that presents various physiological activities. It has been reported that the methylated derivatives of resveratrol show better potential antifungal and antiproliferative activities than resveratrol. In the present study, we investigated the inhibitory effect of 3,5,4′‐trimethoxy‐ trans ‐stilbene (MR‐3), a methylated derivative of resveratrol, on the invasion of A549 cells (a human lung adenocarcinoma cell line). We found that treatment with MR‐3 at the concentration of 5 μM resulted in antiadhesive, antimigratory, and antiinvasive activities on A549 cells through the suppression of matrix metalloproteinase (MMP)‐2 protein expression and transcriptional levels in a time‐dependent manner. The suppression of MMP‐2 expression by MR‐3 led to an inhibition of A549 cell invasion by inactivating phosphorylation of SAPK/c‐Jun N‐terminal kinase (JNK) and p38 MAPK signaling pathways. A time‐dependent inhibition of protein levels for p65, c‐Jun, and c‐Fos in the nucleus by MR‐3 treatment was also observed. In conclusion, our data demonstrate that the antiinvasive effects of MR‐3 on A549 cells are likely mediated through the inhibition of phosphorylation of JNK and p38, as well as a reduction in the protein levels of nuclear factor‐kappa B (NF‐κB) and activator protein‐1 (AP‐1) in the nucleus, ultimately leading to downregulation of MMP‐2 expression.