title: 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.
authors.forename: Derek
authors.initials: D
authors.lastname: Platt
authors.forename: Suneetha
authors.initials: S
authors.lastname: Amara
authors.forename: Toral
authors.initials: T
authors.lastname: Mehta
authors.forename: Koen
authors.initials: K
authors.lastname: Vercuyssee
authors.forename: Elbert L
authors.initials: EL
authors.lastname: Myles
authors.forename: Terrance
authors.initials: T
authors.lastname: Johnson
authors.forename: Venkataswarup
authors.initials: V
authors.lastname: Tiriveedhi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D054377:Chemokine CXCL12 / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology*; D061986:MCF-7 Cells; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D019718:Receptors, CXCR4 / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D007211:Indoles; D061965:Matrix Metalloproteinase Inhibitors; D019718:Receptors, CXCR4; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C063155:violacein