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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Antineoplastic Agents / chemistry
-
Antineoplastic Agents / pharmacology*
-
Blotting, Western
-
Breast Neoplasms / genetics
-
Breast Neoplasms / metabolism
-
Breast Neoplasms / pathology
-
Bridged Bicyclo Compounds, Heterocyclic / chemistry
-
Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
-
Cell Line, Tumor
-
Cell Movement / drug effects
-
Cell Survival / drug effects
-
Chromatin Immunoprecipitation
-
Female
-
Gene Expression / drug effects
-
Humans
-
Imines / chemistry
-
Imines / pharmacology*
-
Immunohistochemistry
-
Mammary Neoplasms, Experimental / pathology
-
Mammary Neoplasms, Experimental / prevention & control
-
Matrix Metalloproteinase 9 / genetics
-
Matrix Metalloproteinase 9 / metabolism*
-
Mice
-
Mice, Inbred BALB C
-
Mice, Nude
-
Molecular Structure
-
Phosphorylation / drug effects
-
Resveratrol
-
Reverse Transcriptase Polymerase Chain Reaction
-
STAT3 Transcription Factor / genetics
-
STAT3 Transcription Factor / metabolism*
-
Stilbenes / chemistry
-
Xenograft Model Antitumor Assays / methods
Substances
-
Antineoplastic Agents
-
Bridged Bicyclo Compounds, Heterocyclic
-
Imines
-
LYR 71
-
STAT3 Transcription Factor
-
Stilbenes
-
Matrix Metalloproteinase 9
-
Resveratrol