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

Xiangsheng Xiao; Bo Chen; Xiaoping Liu; Peng Liu; Guopei Zheng; Feng Ye; Hailin Tang; Xiaoming Xie

doi:10.1371/journal.pone.0112720

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.

Authors

Xiangsheng Xiao¹, Bo Chen¹, Xiaoping Liu¹, Peng Liu¹, Guopei Zheng², Feng Ye¹, Hailin Tang¹, Xiaoming Xie¹

Affiliations

¹ Department of Breast Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China; Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China.
² Affiliated Cancer Hospital and Cancer Research Institute, Guangzhou Medical University, Guangzhou 510095, Guangdong, China.

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.