title: Oral glutamine (AES-14) supplementation inhibits PI-3k/Akt signaling in experimental breast cancer.
abstract: BACKGROUND
  7,12-dimethylbenz [a] anthracene (DMBA) administration to pubertal rats causes breast tumors and inhibits glutathione (GSH) production. Our previous results have established that oral glutamine (GLN) supplementation significantly reduced tumor development, restored the depressed GSH production, and caused a significant decrease in the circulating levels of insulinlike growth factor-1 (IGF-1). The present study was designed to investigate the involvement of the IGF-1-activated phosphatidylinositol 3 kinase (PI-3K)/Akt apoptotic signaling pathway.
  
  
  METHODS
  Forty female Sprague-Dawley rats were randomly divided into 4 groups: DMBA+GLN (n = 16), DMBA+water (n = 8), Oil+GLN (n = 8) and Oil+water (n = 8). At the age of 50 days, rats received a single dose of 100 mg/kg DMBA (n = 24) or sesame oil (n = 16) and were gavaged with a GLN suspension formulation (AES-14) or water for the duration of the entire experiment. The animals were killed 11 weeks after the DMBA application, and the levels of IGF-1, IGF-1 receptor (IGF-IR), Akt, Bcl-2 and Bad in tumorous and nontumorous breast tissue samples were measured by Western blot analysis.
  
  
  RESULTS
  GLN supplementation resulted in a significant decrease in the levels of IGF-1, IGF-IR, Akt, and Bcl-2 in nontumorous samples. At the same time, the levels of pro-apoptotic protein Bad were significantly elevated. The samples collected from tumor tissues showed lower levels of IGF-1, Akt, Bcl-2, Bad, and IGF-IR in comparison with nontumorous tissues.
  
  
  CONCLUSIONS
  GLN supplementation inhibited the PI-3K/Akt pathway that is thought to be important in increasing cell survival during tumorigenesis. These results are in agreement with our hypothesis that GLN counteracts the effects of DMBA and blocks carcinogenesis in vivo.
authors: Division of Breast Surgical Oncology, University of Arkansas for Medical Sciences, Little Rock, Arsansas 72205, USA.
authors: Valentina K
authors: VK
authors: Todorova
authors: Stacy A
authors: SA
authors: Harms
authors: Shaoke
authors: S
authors: Luo
authors: Yihong
authors: Y
authors: Kaufmann
authors: Kirk B
authors: KB
authors: Babb
authors: V Suzanne
authors: VS
authors: Klimberg
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000009:adverse effects; D000230:Adenocarcinoma / Q000139:chemically induced / Q000378:metabolism*; D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D001943:Breast Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D002273:Carcinogens / Q000009:adverse effects; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005973:Glutamine / Q000494:pharmacology*; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000187:drug effects / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects* / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000187:drug effects* / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017451:Receptors, Somatomedin / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects; D016387:Women's Health
chemical_list: D015127:9,10-Dimethyl-1,2-benzanthracene; D015415:Biomarkers; D002273:Carcinogens; D005973:Glutamine; D005978:Glutathione; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2; D017451:Receptors, Somatomedin; C494920:Akt1 protein, rat