LYR71, a derivative of trimeric resveratrol, inhibits tumorigenesis by blocking STAT3-mediated matrix metalloproteinase 9 expression.

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.

• Authors: Ja Eun Kim, 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
• Journal: Experimental & molecular medicine (Exp Mol Med) Vol. 40 Issue 5 Pg. 514-22 (Oct 31 2008) ISSN: 1226-3613 [Print] United States
• PMID: 18985009 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Bridged Bicyclo Compounds, Heterocyclic
• Imines
• LYR 71
• STAT3 Transcription Factor
• Stilbenes
• Matrix Metalloproteinase 9
• Resveratrol

Topics

• Animals
• Antineoplastic Agents (chemistry, pharmacology)
• Blotting, Western
• Breast Neoplasms (genetics, metabolism, pathology)
• Bridged Bicyclo Compounds, Heterocyclic (chemistry, pharmacology)
• 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)
• Resveratrol
• Reverse Transcriptase Polymerase Chain Reaction
• STAT3 Transcription Factor (genetics, metabolism)
• Stilbenes (chemistry)
• Xenograft Model Antitumor Assays (methods)