LYR71, a derivative of trimeric resveratrol, inhibits tumorigenesis by blocking STAT3-mediated matrix metalloproteinase 9 expression.
10.3858/emm.2008.40.5.514
- Author:
Ja Eun KIM
1
;
Hong Sook KIM
;
Yong Jae SHIN
;
Chang Seok LEE
;
Cheolhee WON
;
Sin Ae LEE
;
Jung Weon LEE
;
Youngsoo KIM
;
Jae Seung KANG
;
Sang Kyu YE
;
Myung Hee CHUNG
Author Information
1. Department of Pharmacology, Seoul National University College of Medicine, Seoul, Korea. sangkyu@snu.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
chemokine CCL5;
LYR71;
matrix metalloproteinase 9;
neoplasm metastasis;
STAT3 transcription factor
- MeSH:
Animals;
Antineoplastic Agents/chemistry/*pharmacology;
Bicyclo Compounds, Heterocyclic/chemistry/*pharmacology;
Blotting, Western;
Breast Neoplasms/genetics/metabolism/pathology;
Cell Line, Tumor;
Cell Movement/drug effects;
Cell Survival/drug effects;
Chromatin Immunoprecipitation;
Female;
Gene Expression/drug effects;
Humans;
Imines/chemistry/*pharmacology;
Immunohistochemistry;
Mammary Neoplasms, Experimental/pathology/prevention & control;
Matrix Metalloproteinase 9/genetics/*metabolism;
Mice;
Mice, Inbred BALB C;
Mice, Nude;
Molecular Structure;
Phosphorylation/drug effects;
Reverse Transcriptase Polymerase Chain Reaction;
STAT3 Transcription Factor/genetics/*metabolism;
Stilbenes/chemistry;
Xenograft Model Antitumor Assays/methods
- From:Experimental & Molecular Medicine
2008;40(5):514-522
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.
