title: Chemopreventive Effect of Dietary Glutamineon Colitis-Associated Colorectal Cancer Is Associated with Modulation of the DEPTOR/mTOR Signaling Pathway.
abstract: Glutamine plays a protective role in colitis and colitis-associated colorectal cancer (CAC); however, the protective mechanisms are largely unknown to date. DEP domain-containing mTOR-interacting protein (DEPTOR)/mammalian Target of Rapamycin (mTOR) signaling plays an important role in carcinogenesis. The present study investigated the potential molecular mechanisms for the protective effect of glutamine in a murine model of azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CAC. The effects of glutamine on DEPTOR/mTOR signaling and protein light chain 3 (LC3) were evaluated. Administration of glutamine was associated with attenuated development of CAC. Increased expression of DEPTOR and decreased expressions of factors of mTOR signaling, including phospho-mTOR, phospho-STAT3, phospho-Akt, and phospho-S6, were observed in AOM/DSS mice administered glutamine. Furthermore, oral glutamine was associated with increased LC3-II expression in AOM/DSS mice. The present study indicates that regulation of DEPTOR/mTOR signaling may be an important mechanism for glutamine in prevention against the development of CAC. In addition, the chemopreventive effect of dietary glutamine on CAC is, at least in part, associated with the induction of autophagy.
authors.affiliation: Department of Oncology, the Second Affiliated Hospital of Nanjing Medical University, No. 121 Jiangjiayuan Road, Nanjing 210011, China. summer.cloud@live.cn.
authors.forename: Yun
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Oncology, the Second Affiliated Hospital of Nanjing Medical University, No. 121 Jiangjiayuan Road, Nanjing 210011, China. drkemingwang@sina.cn.
authors.forename: Keming
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Oncology, the Second Affiliated Hospital of Nanjing Medical University, No. 121 Jiangjiayuan Road, Nanjing 210011, China. drfanyingrui@sohu.com.
authors.forename: Yingrui
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Pathology, the Second Affiliated Hospital of Nanjing Medical University, No. 121 Jiangjiayuan Road, Nanjing 210011, China. dryanwang@sina.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Intensive Care Unit, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China. drliqunsun@sina.com.
authors.forename: Liqun
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Oncology, the Second Affiliated Hospital of Nanjing Medical University, No. 121 Jiangjiayuan Road, Nanjing 210011, China. lixiang@kplink.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Oncology, the Second Affiliated Hospital of Nanjing Medical University, No. 121 Jiangjiayuan Road, Nanjing 210011, China. rabbitwjr@126.com.
authors.forename: Jirong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Oncology, the Second Affiliated Hospital of Nanjing Medical University, No. 121 Jiangjiayuan Road, Nanjing 210011, China. zhaoxiawang88@hotmail.com.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Oncology, the Second Affiliated Hospital of Nanjing Medical University, No. 121 Jiangjiayuan Road, Nanjing 210011, China. ljsmz1229@163.com.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: Emergency Center, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China. xzmcyy@163.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Institute of Digestive Endoscopy and Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, No. 121 Jiangjiayuan Road, Nanjing 210011, China. drjiguozhong@sina.com.
authors.forename: Guozhong
authors.initials: G
authors.lastname: Ji
mesh_terms: D000818:Animals; D003092:Colitis / Q000150:complications*; D015179:Colorectal Neoplasms / Q000209:etiology / Q000517:prevention & control*; D004032:Diet; D005786:Gene Expression Regulation / Q000187:drug effects; D005973:Glutamine / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C570841:deptor protein, mouse; D005973:Glutamine; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases
keywords: DEPTOR; colitis; colorectal cancer; glutamine; mTOR signaling