Dietary walnuts inhibit colorectal cancer growth in mice by suppressing angiogenesis

January 1, 2012 Human Health and Nutrition Data 0 Comments

Dietary walnuts inhibit colorectal cancer growth in mice by suppressing angiogenesis

Year: 2012
Authors: Nagel, J.M. Brinkoetter, M. Magkos, F. Liu, X. Chamberland, J.P. Shah, S. Zhou, J.
Publication Name: Nutrition
Publication Details: doi: 10.1016/j.nut.2011.03.004


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. HT-29 human colon cancer cells were injected in 6-wk-old female nude mice. After a 1 wk acclimation period, mice (n of 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. 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).  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 abstract).
The results of several large-scale epidemiological studies in humans show an inverse association between nut and seed consumption and the incidence of colorectal cancer. Animal studies examining the effect of flaxseed (linseed) supplementation on the formation of precancerous colorectal lesions and the growth of chemically induced colorectal tumors reported beneficial effects. However, the underlying mechanisms remain unclear and poorly described. The purpose of the present study was to comparatively investigate the effect of isoenergetic amounts of walnuts and flaxseed oil in the diet on colorectal cancer growth rate in mice in vivo and to explore relevant underlying molecular mechanisms. The results showed that isocaloric amounts of walnuts and flaxseed oil, compared with corn oil, inhibited colorectal cancer growth rate by 30% to 45%, and that tumor weight decreased accordingly. Large central areas of necrosis in the tumors of sacrificed mice on both walnut and flaxseed diets, despite their smaller overall size and weight at autopsy, were noted which is indicative of insufficient blood supply. Walnuts and flaxseed oil intake reduced expression levels of several angiogenic proteins including VEGF, but does not affect mediators of apoptosis and proliferation in serum, such as insulin, IGF-1, and IGFBPs, or markers of inflammation and antioxidant capacity. Accordingly, angiogenesis within viable tissue was significantly reduced in walnut-fed mice. Compared with control tumors, tumors from walnut- and flaxseed oil-fed mice had larger central necrotic areas despite their smaller size. The extensive central necrosis following walnut and flaxseed consumption is indicative of a considerably impaired capacity to maintain sufficient nutrient and oxygen supply via the bloodstream, even at a much slower growth rate than control tumors. Consumption of flaxseed oil suppresses the growth rate of established colorectal cancer in vivo, reduces VEGF, and leads to extensive central necrosis. The reduction in serum angiogenic factors appeared to be greater overall in the flaxseed oil than the walnut diet group. Walnuts and flaxseed are particularly rich sources of ALA.  In summary, this study investigated the effects of dietary supplementation with isoenergetic amounts of walnuts or flaxseed oil on established colorectal cancer in mice in vivo and found significant inhibition of cancer growth rate and reduction in tumor weight, compared with a corn oil-based control diet. Extensive central necrosis in tumors from walnut fed and flaxseed oil-fed animals was found. Impaired angiogenesis appears to underlie the antitumorigenic effects of dietary walnuts and flaxseed oil (Editors comments).

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