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.
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 muM 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-kappaB) and activator protein-1 (AP-1) in the nucleus, ultimately leading to downregulation of MMP-2 expression.
Yang
Ya-Ting
YT
Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan.
Weng
Chia-Jui
CJ
Ho
Chi-Tang
CT
Yen
Gow-Chin
GC
D000230:Adenocarcinoma / Q000201:enzymology* / Q000473:pathology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D016328:NF-kappa B / Q000032:analysis / Q000037:antagonists & inhibitors; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000032:analysis / Q000037:antagonists & inhibitors; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
C497286:3,4',5-trimethoxystilbene; D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D012333:RNA, Messenger; D013267:Stilbenes; D018808:Transcription Factor AP-1; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2