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DADS Suppresses Human Esophageal Xenograft Tumors through RAF/MEK/ERK and Mitochondria-Dependent Pathways

Authors :
Xiaoran Yin
Jun Zhang
Xiaoning Li
Dong Liu
Cheng Feng
Rongrui Liang
Kun Zhuang
Chenlei Cai
Xinghuan Xue
Fuchun Jing
Xijing Wang
Jun Wang
Xinlian Liu
Hongbing Ma
Source :
International Journal of Molecular Sciences, Vol 15, Iss 7, Pp 12422-12441 (2014)
Publication Year :
2014
Publisher :
MDPI AG, 2014.

Abstract

Diallyl disulfide (DADS) is a natural organosulfur compound isolated from garlic. DADS has various biological properties, including anticancer, antiangiogenic, and antioxidant effects. However, the anticancer mechanisms of DADS in human esophageal carcinoma have not been elucidated, especially in vivo. In this study, MTT assay showed that DADS significantly reduced cell viability in human esophageal carcinoma ECA109 cells, but was relatively less toxic in normal liver cells. The pro–apoptotic effect of DADS on ECA109 cells was detected by Annexin V-FITC/propidium iodide (PI) staining. Flow cytometry analysis showed that DADS promoted apoptosis in a dose-dependent manner and the apoptosis rate could be decreased by caspase-3 inhibitor Ac-DEVD-CHO. Xenograft study in nude mice showed that DADS treatment inhibited the growth of ECA109 tumor in both 20 and 40 mg/kg DADS groups without obvious side effects. DADS inhibited ECA109 tumor proliferation by down-regulating proliferation cell nuclear antigen (PCNA). DADS induced apoptosis by activating a mitochondria-dependent pathway with the executor of caspase-3, increasing p53 level and Bax/Bcl-2 ratio, and downregulating the RAF/MEK/ERK pathway in ECA109 xenograft tumosr. Based on studies in cell culture and animal models, the findings here indicate that DADS is an effective and safe anti-cancer agent for esophageal carcinoma.

Details

Language :
English
ISSN :
14220067
Volume :
15
Issue :
7
Database :
Directory of Open Access Journals
Journal :
International Journal of Molecular Sciences
Publication Type :
Academic Journal
Accession number :
edsdoj.baece073b73f4dc68312af9905da5586
Document Type :
article
Full Text :
https://doi.org/10.3390/ijms150712422