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Int. J. Mol. Sci. 2014, 15(7), 12422-12441;

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

Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
Department of Digestion, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
Department of Oncology, the First Affiliated Hospital of Soochow University, No. 188, Shizi Street, Suzhou 215006, China
Department of Digestion, Xi'an Central Hospital, Xi'an 710003, China
Department of Digestive Diseases, Baoji People's Hospital, Baoji 721000, China
Department of Gastroenterology, Xi'an Hospital of Traditional Chinese Medicine, Xi'an 710001, China
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Received: 5 May 2014 / Revised: 22 June 2014 / Accepted: 7 July 2014 / Published: 14 July 2014
(This article belongs to the Special Issue Molecular Science for Drug Development and Biomedicine)
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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. View Full-Text
Keywords: esophageal carcinoma; DADS; apoptosis; animal model esophageal carcinoma; DADS; apoptosis; animal model

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Yin, X.; Zhang, J.; Li, X.; Liu, D.; Feng, C.; Liang, R.; Zhuang, K.; Cai, C.; Xue, X.; Jing, F.; Wang, X.; Wang, J.; Liu, X.; Ma, H. DADS Suppresses Human Esophageal Xenograft Tumors through RAF/MEK/ERK and Mitochondria-Dependent Pathways. Int. J. Mol. Sci. 2014, 15, 12422-12441.

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