title: Diallyl disulfide inhibits growth and metastatic potential of human triple-negative breast cancer cells through inactivation of the β-catenin signaling pathway.
abstract: METHODS
  Although 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.
  
  
  RESULTS
  We 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 β-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 β-catenin was decreased, and the downstream molecules were dysregulated.
  
  
  CONCLUSIONS
  Our results show that the antitumor effect of DADS on TNBC cells is mediated by the β-catenin pathway, suggesting that DADS could be used as a potential therapeutic agent for treating or preventing breast cancer.
authors.affiliation: Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.affiliation: Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P. R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Yang
authors.affiliation: Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P. R. China.
authors.forename: Tingxiu
authors.initials: T
authors.lastname: Xiang
authors.affiliation: Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P. R. China.
authors.forename: Weiyan
authors.initials: W
authors.lastname: Peng
authors.affiliation: Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P. R. China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Qiu
authors.affiliation: Department of Pharmacology, Chongqing Medical University, Chongqing, P. R. China.
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Wan
authors.affiliation: Department of Pathophysiology, Chongqing Medical University, Chongqing, P. R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P. R. China.
authors.forename: Hongyuan
authors.initials: H
authors.lastname: Li
authors.affiliation: Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P. R. China.
authors.forename: Hongzhong
authors.initials: H
authors.lastname: Li
authors.affiliation: Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P. R. China.
authors.forename: Guosheng
authors.initials: G
authors.lastname: Ren
mesh_terms: D000498:Allyl Compounds / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004220:Disulfides / Q000494:pharmacology*; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005260:Female; D005737:Garlic / Q000737:chemistry*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D015398:Signal Transduction; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000498:Allyl Compounds; D000970:Antineoplastic Agents; C494826:BAX protein, human; D004220:Disulfides; D051028:bcl-2-Associated X Protein; D051176:beta Catenin; C028009:diallyl disulfide; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Diallyl disulfide; Epithelial-mesenchymal transition; Matrix metalloproteinase; Triple-negative breast cancer; β-catenin