Document Detail

Violacein inhibits matrix metalloproteinase mediated CXCR4 expression: Potential anti-tumor effect in cancer invasion and metastasis.
MedLine Citation:
PMID:  25450700     Owner:  NLM     Status:  Publisher    
Matrix metalloproteinases (MMP-2 and -9) play an important role in the tumor metastasis through cleavage of proinflammatory cytokines. Violacein a small molecule produced by Chromobacterium violaceum and has been implicated with anti-cancer effects. In this study we investigated the molecular basis of violacein mediated downregulation of CXCL12/CXCR4, chemokine-receptor ligand interaction. Zymography analysis demonstrated that violacein significantly inhibited the cytokine (TNFα and TGFβ) mediated MMP-2 activation in MCF-7 breast cancer cell line. MMP-2 plays a critical role in the secretion of inflammatory chemokine, CXCL12, involved in cell migration and cancer metastasis. ELISA analysis demonstrated that violacein inhibited the secretion of CXCL12 from the activated MCF-7 cells. Further, we show that MMP-2/-9 act synergistically at two distinct steps towards the membrane expression of the tumor metastasis chemokine receptor, CXCR4. Violacein efficiently downregulated the CXCR4 membrane expression through MMP-9 inhibition. Taken together, these studies demonstrate a unique anti-tumor mechanism of action of violacein through reduction of CXCL12/CXCR4 interaction. These studies could offer a novel venue for violacein in cancer therapy.
Derek Platt; Suneetha Amara; Toral Mehta; Koen Vercuyssee; Elbert L Myles; Terrance Johnson; Venkataswarup Tiriveedhi
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-10-30
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  455     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2014 Oct 
Date Detail:
Created Date:  2014-12-3     Completed Date:  -     Revised Date:  2014-12-3    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  -    
Other Details:
Languages:  ENG     Pagination:  107-112     Citation Subset:  -    
Copyright Information:
Copyright © 2014 Elsevier Inc. All rights reserved.
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