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• W2166260429 abstract "Tissue inhibitor of metalloproteinase-2 (TIMP-2), the endogenous inhibitor of matrix metalloproteinase-2 (MMP-2), regulates tumor invasion by modulating the activity of MMP-2. In addition, TIMP-2 is involved in the direct regulation of cell growth and angiogenesis, independent of MMP inhibition. Therefore, the development of therapeutic agents that increase TIMP-2 levels may offer a novel and broad approach to anti-neoplastic therapy. We report that a novel small molecule synthetic flavanoid SR13179, which inhibits the invasion of a highly metastatic human breast cancer cell line MCF-10CA1a through Matrigel, significantly increases protein and mRNA levels of TIMP-2 in a time- and dose-dependent manner. SR13179 inhibits the gelatinolytic activity of MMP-2 by >50% but has no effect on MMP-2 protein expression. SR13179 also possesses potent anti-tumor activity in several tumor cell lines regardless of their hormone receptor, p53 or multi-drug resistance status. Given the multifunctional inhibitory activity of TIMP-2 on tumor growth and invasion, the observed increase in TIMP-2 expression by SR13179 may play a central role in the anti-tumor and anti-invasive activity of this novel small molecule. Modulation of TIMP-2 protein expression may be a new molecular target for anti-metastatic adjuvant therapy for breast and other cancers." @default.
• W2166260429 created "2016-06-24" @default.
• W2166260429 creator A5032668570 @default.
• W2166260429 creator A5056437073 @default.
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• W2166260429 date "2010-03-01" @default.
• W2166260429 modified "2023-09-26" @default.
• W2166260429 title "Increase in tissue inhibitor of metalloproteinase-2 (TIMP-2) levels and inhibition of MMP-2 activity in a metastatic breast cancer cell line by an anti-invasive small molecule SR13179" @default.
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• W2166260429 doi "https://doi.org/10.1016/j.canlet.2009.08.006" @default.
• W2166260429 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19751965" @default.
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