Diallyl Trisulfide Modulates Notch Pathway Components in Breast Cancer Cells
Breast cancer affects one in eight women throughout the course of their lifetimes creating an immediate demand for novel prevention strategies against this disease. The Notch signaling pathway is often aberrantly activated in human malignancies including breast cancer. Alpha secretases, including A Disintegrin and Metalloprotease (ADAM)-10 and -17, are proteases that play a key role in the cleavage of cell surface molecules and subsequent ligand-mediated activation of Notch signaling pathway. High expression levels of ADAM10 are clinically associated with lower disease-free survival in breast cancer patients. The goal of this study was to determine the effect of diallyl trisulfide (DATS), a bioactive organosulfide found in garlic and other Allium vegetables, on Notch pathway components, specifically alpha secretases, in an in vitro model of breast cancer. Here we report for the first time that DATS inhibits the expression of ADAM10 and ADAM17 in estrogen-independent MDA-MB-231 and estrogen-dependent MCF-7 breast cancer cells, as well as in Harvey-ras (H-Ras) transformed MCF10A-H-Ras breast epithelial cells. We also show that DATS inhibits the Notch ligands Jagged-1 and Jagged-2. Furthermore, we show that DATS treatment reduces overall cell viability in MDA-MB-231, MCF-7 and MCF10A-H-Ras cells, and that DATS treatment reduces viability of normal-like breast epithelial MCF-12A cells to a lesser extent. DATS induces a dose-dependent reduction in colony formation ability of MDA-MB-231 and MCF-7 breast cancer cells. Collectively, our results show that DATS modulates Notch pathway components deregulated in breast cancer cells and may serve as a functionally relevant bioactive for breast cancer prevention.
Stan, Purdue University.
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