Diallyl disulfide suppresses SRC/Ras/ERK signaling-mediated proliferation and metastasis in human breast cancer by up-regulating miR-34a.
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.
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.
Xiangsheng
X
Xiao
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.
Bo
B
Chen
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.
Xiaoping
X
Liu
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.
Peng
P
Liu
Affiliated Cancer Hospital and Cancer Research Institute, Guangzhou Medical University, Guangzhou 510095, Guangdong, China.
Guopei
G
Zheng
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.
Feng
F
Ye
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.
Hailin
H
Tang
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.
Xiaoming
X
Xie
D000498:Allyl Compounds / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects*; D004220:Disulfides / Q000032:analysis / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008156:Luciferases; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D010957:Plasmids / Q000235:genetics; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects*; D013440:Sulfides / Q000737:chemistry
D000498:Allyl Compounds; D004220:Disulfides; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D013440:Sulfides; C028009:diallyl disulfide; C038491:allyl sulfide; D008156:Luciferases