TY - JOUR

T1 - Dietary walnuts inhibit colorectal cancer growth in mice by suppressing angiogenesis

AU - Nagel, Jutta M

AU - Brinkoetter, Mary

AU - Magkos, Faidon

AU - Liu, Xiaowen

AU - Chamberland, John P

AU - Shah, Sunali

AU - Zhou, Jinrong

AU - Blackburn, George

AU - Mantzoros, Christos S

N1 - Published by Elsevier Inc.

PY - 2012

Y1 - 2012

N2 - 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).Conclusion: 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.

AB - 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).Conclusion: 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.

KW - Angiogenesis Inhibitors/therapeutic use

KW - Animals

KW - Antigens, CD34/metabolism

KW - Antineoplastic Agents, Phytogenic/therapeutic use

KW - Colorectal Neoplasms/blood

KW - Dietary Supplements

KW - Female

KW - HT29 Cells

KW - Humans

KW - Juglans

KW - Linseed Oil/therapeutic use

KW - Mice

KW - Mice, Nude

KW - Necrosis

KW - Neovascularization, Pathologic/prevention & control

KW - Nuts

KW - Random Allocation

KW - Tumor Burden

KW - Vascular Endothelial Growth Factors/blood

KW - Xenograft Model Antitumor Assays

U2 - 10.1016/j.nut.2011.03.004

DO - 10.1016/j.nut.2011.03.004

M3 - Journal article

C2 - 21795022

VL - 28

SP - 67

EP - 75

JO - Nutrition

JF - Nutrition

SN - 0899-9007

IS - 1

ER -