4.7 Article

Diallyl disulfide inhibits growth and metastatic potential of human triple-negative breast cancer cells through inactivation of the -catenin signaling pathway

Journal

MOLECULAR NUTRITION & FOOD RESEARCH
Volume 59, Issue 6, Pages 1063-1075

Publisher

WILEY
DOI: 10.1002/mnfr.201400668

Keywords

-catenin; Diallyl disulfide; Epithelial-mesenchymal transition; Matrix metalloproteinase; Triple-negative breast cancer

Funding

  1. National Natural Science Foundation of China [81472475, 81102007]
  2. International S&T Cooperation Program of China (ISTCP) [2012DFA10650]
  3. National High Technology Research and Development Program of China (863 Program) [2012AA020101]

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ScopeAlthough diallyl disulfide (DADS), an important garlic (Allium sativum) derivative, has exhibited potential anticancer activity, the molecular mechanism of this activity remains unknown. In this study, we evaluated the antitumor activity of DADS in triple-negative breast cancer (TNBC) cell lines based in vitro and in vivo models. Methods and resultsWe found that treatment with DADS resulted in decreased viability, increased apoptosis, and suppression of metastatic potential in TNBC cells. Furthermore, DADS induced dysregulation of B-cell lymphoma (Bcl)-2 family members, downregulation of matrix metalloproteinase (MMP)-9 and reversal of the epithelial-mesenchymal transition (EMT). Interestingly, DADS significantly inhibited activation of the -catenin signaling pathway, which regulated Bcl-2 family members, MMP-9 and EMT in TNBC cells. Consistent with these in vitro findings, we also verified the anticancer potential of DADS in MDA-MB-231 xenograft mice. Treatment with DADS significantly reduced tumor volume and weight and increased apoptosis in these mice, while the expression of active -catenin was decreased, and the downstream molecules were dysregulated. ConclusionOur results show that the antitumor effect of DADS on TNBC cells is mediated by the -catenin pathway, suggesting that DADS could be used as a potential therapeutic agent for treating or preventing breast cancer.

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