title: Dietary walnuts inhibit colorectal cancer growth in mice by suppressing angiogenesis.
abstract: OBJECTIVE
  Animal studies have demonstrated that dietary supplementation with flaxseed oil inhibits colorectal cancer growth. Recent data indicate that walnuts have strong antiproliferative properties against colon cancer cells in vitro but no previous study has assessed the effects of walnuts in vivo or performed a joint evaluation of flaxseed oil and walnuts. The aim of the present study was to examine the effect of dietary walnuts on colorectal cancer in vivo and to comparatively evaluate their efficacy in relation to flaxseed oil.
  
  
  METHODS
  HT-29 human colon cancer cells were injected in 6-wk-old female nude mice. After a 1-wk acclimation period, mice (n = 48) were randomized to diets containing ∼19% of total energy from walnuts, flaxseed oil, or corn oil (control) and were subsequently studied for 25 d.
  
  
  RESULTS
  Tumor growth rate was significantly slower in walnut-fed and flaxseed-fed mice compared with corn oil-fed animals (P < 0.05) by 27% and 43%, respectively. Accordingly, final tumor weight was reduced by 33% and 44%, respectively (P < 0.05 versus control); the differences between walnut and flaxseed diets did not reach significance. We found no differences among groups in metabolic and hormonal profile, serum antioxidant capacity, or inflammation (P > 0.05). However, walnuts and flaxseed oil significantly reduced serum expression levels of angiogenesis factors, including vascular endothelial growth factor (by 30% and 80%, respectively), and approximately doubled total necrotic areas despite smaller tumor sizes (P < 0.05 versus control). Dietary walnuts significantly decreased angiogenesis (CD34 staining; P = 0.017 versus control), whereas this effect did not reach significance in the flaxseed oil group (P = 0.454 versus control).
  
  
  CONCLUSIONS
  We conclude that walnuts in the diet inhibit colorectal cancer growth by suppressing angiogenesis. Further studies are needed to confirm our findings in humans and explore underlying mechanisms.
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Jutta M
authors.initials: JM
authors.lastname: Nagel
authors.forename: Mary
authors.initials: M
authors.lastname: Brinkoetter
authors.forename: Faidon
authors.initials: F
authors.lastname: Magkos
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Liu
authors.forename: John P
authors.initials: JP
authors.lastname: Chamberland
authors.forename: Sunali
authors.initials: S
authors.lastname: Shah
authors.forename: Jinrong
authors.initials: J
authors.lastname: Zhou
authors.forename: George
authors.initials: G
authors.lastname: Blackburn
authors.forename: Christos S
authors.initials: CS
authors.lastname: Mantzoros
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000097:blood / Q000178:diet therapy* / Q000378:metabolism / Q000473:pathology; D019587:Dietary Supplements; D005260:Female; D019073:HT29 Cells; D006801:Humans; D031324:Juglans; D008043:Linseed Oil / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D009336:Necrosis; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D009754:Nuts; D011897:Random Allocation; D047368:Tumor Burden; D042442:Vascular Endothelial Growth Factors / Q000097:blood; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D018952:Antigens, CD34; D000972:Antineoplastic Agents, Phytogenic; D042442:Vascular Endothelial Growth Factors; D008043:Linseed Oil