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KMID : 0620920080400050514
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Experimental & Molecular Medicine
2008 Volume.40 No. 5 p.514 ~ p.522
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LYR7, a derivative of trimeric resveratrol, inhibits tumorigenesis by blocking STAT3-mediated matrix metalloproteinase 9 expression
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Kim Ja-Eun
Kang Jae-Seung
Ye Sang-Gyu
Chung Myung-Hee
Kim Hong-Sook
Lee Chang-Seok
Won Cheol-Hee
Lee Sin-Ae
Lee Weon
Kim Young-Soo
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Abstract
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Tumor migration/invasion is the main cause of tumor progression and STAT3 is needed to enhance tumor migration/invasion by up-regulating MMP-9. Thus, agents that inhibit STAT3 activation may be used as an anticancer drug. We present herein that 6-methyl-2-propylimino-6, 7-dihydro-5H-benzo [1, 3]-oxathiol- 4-one (LYR71) , a derivative of trimeric resveratrol, has an anticancer activity through inhibition of STAT3 activation. We found that LYR71 suppressed STAT3 activation and inhibited the expression and activity of MMP-9 in RANTES-stimulated breast cancer cells. In addition, LYR71 reduced RANTES-induced MMP-9 transcripts by blocking STAT3 recruitment, dissociating p300 and deacetylating histone H3 and H4 on the MMP-9 promoter. Furthermore, LYR71 inhibited tumor migration/invasion in RANTES-treated breast cancer cells and consequently blocked tumor progression in tumor-bearing mice. Taken together, the results of this study suggest that LYR71 can be therapeutically useful due to the inhibition effect of STAT3-mediated MMP-9 expression in breast cancer cells.
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KEYWORD
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chemokine CCL5, LYR71, matrix metalloproteinase 9, neoplasm metastasis, STAT3 transcription factor
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