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Violacein inhibits matrix metalloproteinase mediated CXCR4 expression: potential anti-tumor effect in cancer invasion and metastasis.

Abstract：

: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.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Platt D,Amara S,Mehta T,Vercuyssee K,Myles EL,Johnson T,Tiriveedhi V

doi

10.1016/j.bbrc.2014.10.124

subject

Has Abstract

pub_date

2014-12-05 00:00:00

pages

107-12

issue

1-2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(14)01944-5

journal_volume

455

pub_type

杂志文章

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