Diallyl disulfide suppresses SRC/Ras/ERK signaling-mediated proliferation and metastasis in human breast cancer by up-regulating miR-34a

PLoS One. 2014 Nov 14;9(11):e112720. doi: 10.1371/journal.pone.0112720. eCollection 2014.

Abstract

Diallyl disulfide (DADS) is one of the major volatile components of garlic oil. DADS has various biological properties, including anticancer, antiangiogenic, and antioxidant effects. However, the anticancer mechanisms of DADS in human breast cancer have not been elucidated, particularly in vivo. In this study, we demonstrated that the expression of miR-34a was up-regulated in DADS-treated MDA-MB-231 cells. miR-34a not only inhibited breast cancer growth but also enhanced the antitumor effect of DADS, both in vitro and in vivo. Furthermore, Src was identified as a target of miR-34a, with miR-34a inhibiting SRC expression and consequently triggering the suppression of the SRC/Ras/ERK pathway. These results suggest that DADS could be a promising anticancer agent for breast cancer. miR-34a may also demonstrate a potential gene therapy agent that could enhance the antitumor effects of DADS.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Allyl Compounds / analysis
  • Allyl Compounds / chemistry
  • Allyl Compounds / pharmacology*
  • Analysis of Variance
  • Animals
  • Blotting, Western
  • Breast Neoplasms / drug therapy*
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / drug effects*
  • Disulfides / analysis
  • Disulfides / pharmacology*
  • Female
  • Gene Expression Regulation / drug effects*
  • Gene Expression Regulation / genetics
  • Humans
  • Immunohistochemistry
  • Luciferases
  • Mice
  • MicroRNAs / metabolism*
  • Neoplasm Metastasis / prevention & control*
  • Plasmids / genetics
  • RNA Interference
  • Signal Transduction / drug effects*
  • Sulfides / chemistry

Substances

  • Allyl Compounds
  • Disulfides
  • MIRN34 microRNA, human
  • MicroRNAs
  • Sulfides
  • diallyl disulfide
  • allyl sulfide
  • Luciferases

Grants and funding

This work was supported by funds from the National Natural Science Foundation of China (81472575, 81472469, 31100935, 81272514, 81302318, 81372133, and 81301798), the Key Programme of the National Natural Science Foundation of China (31030061), the China Postdoctoral Science Foundation (2012M520075 and 2014M550447), and the Science and Technology Planning Project of Guangzhou (2014J4100169). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.