LYR71, a derivative of trimeric resveratrol, inhibits tumorigenesis by blocking STAT3-mediated matrix metalloproteinase 9 expression.
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.
Kim
Ja Eun
JE
Department of Pharmacology, Seoul National University College of Medicine, Seoul 110-799, Korea.
Kim
Hong Sook
HS
Shin
Yong Jae
YJ
Lee
Chang Seok
CS
Won
Cheolhee
C
Lee
Sin Ae
SA
Lee
Jung Weon
JW
Kim
Youngsoo
Y
Kang
Jae Seung
JS
Ye
Sang Kyu
SK
Chung
Myung Hee
MH
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D047369:Chromatin Immunoprecipitation; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007097:Imines / Q000737:chemistry / Q000494:pharmacology*; D007150:Immunohistochemistry; D008325:Mammary Neoplasms, Experimental / Q000473:pathology / Q000517:prevention & control; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015394:Molecular Structure; D010766:Phosphorylation / Q000187:drug effects; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D013267:Stilbenes / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007097:Imines; C530478:LYR 71; D050796:STAT3 Transcription Factor; D013267:Stilbenes; D020780:Matrix Metalloproteinase 9; D000077185:Resveratrol