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- W2565723003 abstract "Matrix metalloproteinases (MMP-2 and -9) play an important role in the tumor metastasis through cleavage of proinflammatory chemokines. Violacein a small molecule naturally produced by Chromobacterium violaceum has been implicated with anti-tumor effects. In this study we investigated the molecular basis of violacein mediated downregulation of CXCL12-CXCR4, chemokine-receptor expression. Gelatin 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 CXCL12 a cell migration chemokine. ELISA analysis demonstrated that violacein induced significantly decreased secretion of CXCL12 from cytokine induced MCF-7 cells. Further, we show that MMP-2 and MMP-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 the unique mechanism of action of violacein towards potential anti-tumor effect through reduction of CXCL12-CXCR4 expression by inhibition of proteolytic MMP activity. Based on these studies violacein could offer a novel therapeutic venue in cancer therapy. Citation Format: Venkataswarup Tiriveedhi. Violacein inhibits matrix metalloproteinase mediated CXCR4 expression: Potential anti-tumor effect in cancer invasion and metastasis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5561. doi:10.1158/1538-7445.AM2015-5561" @default.
- W2565723003 created "2017-01-06" @default.
- W2565723003 creator A5057225912 @default.
- W2565723003 date "2015-08-01" @default.
- W2565723003 modified "2023-09-26" @default.
- W2565723003 title "Abstract 5561: Violacein inhibits matrix metalloproteinase mediated CXCR4 expression: Potential anti-tumor effect in cancer invasion and metastasis" @default.
- W2565723003 doi "https://doi.org/10.1158/1538-7445.am2015-5561" @default.
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