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.
Highlights
Significant efforts and intense investigations have been made to fight colorectal cancer (CRC) over the recent decades, CRC still ranks second in cancer-related deaths worldwide.More than 1.2 million patients are diagnosed with CRC, and greater than 600,000 deaths per year occur as a result of this disease
We aimed to explore the regulatory role of GLN on the DEPTOR-Mammalian Target of Rapamycin (mTOR) signaling pathway in an animal model of CAC
We investigated the effects of oral GLN on the DEPTOR target protein mTOR
Summary
Significant efforts and intense investigations have been made to fight colorectal cancer (CRC) over the recent decades, CRC still ranks second in cancer-related deaths worldwide. More than 1.2 million patients are diagnosed with CRC, and greater than 600,000 deaths per year occur as a result of this disease. Chronic inflammation in the intestine ranks among the top three high-risk conditions for CRC, and inflammatory bowel disease (IBD) is an important risk factor for human CRC. Deregulation of the mTOR signaling pathway has been demonstrated in a variety of human cancers, including CRC [7,8]. It was recently demonstrated that both mTOR complexes are directly inhibited by DEP domain-containing mTOR-interacting protein (DEPTOR), which binds and inhibits mTOR through a PDZ domain [9]
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