title: DADS suppresses human esophageal xenograft tumors through RAF/MEK/ERK and mitochondria-dependent pathways.
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.
authors.affiliation: Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China. yinxiaoran@163.com.
authors.forename: Xiaoran
authors.initials: X
authors.lastname: Yin
authors.affiliation: Department of Digestion, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China. jun3z@163.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China. qingcao0066@163.com.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Digestion, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China. liudong_doc@163.com.
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Digestion, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China. fc_2004188@163.com.
authors.forename: Cheng
authors.initials: C
authors.lastname: Feng
authors.affiliation: Department of Oncology, the First Affiliated Hospital of Soochow University, No. 188, Shizi Street, Suzhou 215006, China. lengbeng@hotmail.com.
authors.forename: Rongrui
authors.initials: R
authors.lastname: Liang
authors.affiliation: Department of Digestion, Xi'an Central Hospital, Xi'an 710003, China. zhuanger6695@sohu.com.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhuang
authors.affiliation: Department of Digestion, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China. cchenlei2007@163.com.
authors.forename: Chenlei
authors.initials: C
authors.lastname: Cai
authors.affiliation: Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China. xuexinghuan1962@163.com.
authors.forename: Xinghuan
authors.initials: X
authors.lastname: Xue
authors.affiliation: Department of Digestive Diseases, Baoji People's Hospital, Baoji 721000, China. fleming7798@163.com.
authors.forename: Fuchun
authors.initials: F
authors.lastname: Jing
authors.affiliation: Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China. wangxijingxian@126.com.
authors.forename: Xijing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Xi'an Hospital of Traditional Chinese Medicine, Xi'an 710001, China. wangjuntaiji@126.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China. liuxldoc@yeah.net.
authors.forename: Xinlian
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China. mhbxian@126.com.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Ma
mesh_terms: D000498:Allyl Compounds / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D004220:Disulfides / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D008819:Mice, Nude; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000498:Allyl Compounds; D000970:Antineoplastic Agents; D004220:Disulfides; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C028009:diallyl disulfide; D053148:Caspase 3