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Walnuts Have Potential For Cancer Prevention And Treatment In Mice

By W. Elaine Hardman

BACKGROUND
Cancer may not be completely the result of novel or inherited genetic mutations but may in fact be a largely preventable disease. Researchers have identified biochemicals, including n–3 (ω-3) fatty acids, tocopherols, β-sitosterol, and pedunculagin, that are found in walnuts and that have cancer-prevention properties. Mouse studies in which walnuts were added to the diet have shown the following compared with the control diet: 1) the walnut-containing diet inhibited the growth rate of human breast cancers implanted in nude mice by ∼80%; 2) the walnut-containing diet reduced the number of mammary gland tumors by ∼60% in a transgenic mouse model; 3) the reduction in mammary gland tumors was greater with whole walnuts than with a diet containing the same amount of n–3 fatty acids, supporting the idea that multiple components in walnuts additively or synergistically contribute to cancer suppression; and 4) walnuts slowed the growth of prostate, colon, and renal cancers by antiproliferative and antiangiogenic mechanisms. Cell studies have aided in the identification of the active components in walnuts and of their mechanisms of action. This review summarizes these studies and presents the notion that walnuts may be included as a cancer-preventive choice in a healthy diet.
*Preliminary animal research has been investigating the potential benefit walnuts may have on fighting a variety of cancers including breast, prostate, and colorectal. Please note, that these animal studies are provided as background and used to formulate hypotheses for additional research needed to determine the effects on humans.

PUBLISHED : JANUARY 1, 2014
STUDY TYPE : ANIMAL FEEDING STUDY
TOPICS : CANCER, BREAST CANCER
SOURCE : http://jn.nutrition.org/cgi/rapidpdf/jn.113.188466?ijkey=MEM0MP2luOBBc&keytype=ref&siteid=nutrition

Diet Components Can Suppress Inflammation And Reduce Cancer Risk

By W. Elaine Hardman

BACKGROUND
Epidemiology studies indicate that diet or specific dietary components can reduce the risk for cancer, cardiovascular disease and diabetes. An underlying cause of these diseases is chronic inflammation. Dietary components that are beneficial against disease seem to have multiple mechanisms of action and many also have a common mechanism of reducing inflammation, often via the NFκB pathway. Thus, a plant based diet can contain many components that reduce inflammation and can reduce the risk for developing all three of these chronic diseases.

OBJECTIVE
We summarize dietary components that have been shown to reduce cancer risk and two studies that show that dietary walnut can reduce cancer growth and development.

DESIGN
Part of the mechanism for the anticancer benefit of walnut was by suppressing the activation of NFκB.

RESULT
In this brief review, we focus on reduction of cancer risk by dietary components and the relationship to suppression of inflammation. However, it should be remembered that most dietary components have multiple beneficial mechanisms of action that can be additive and that suppression of chronic inflammation should reduce the risk for all three chronic diseases.

PUBLISHED : JUNE 8, 2014
STUDY TYPE : SCIENTIFIC MEETING PROCEEDINGS
TOPIC : CANCER
SOURCE : http://e-nrp.org/DOIx.php?id=10.4162/nrp.2014.8.3.233

Communicating Clinical Research To Reduce Cancer Risk Through Diet: Walnuts As A Case Example

By Cheryl D. Toner

BACKGROUND
Inflammation is one mechanism through which cancer is initiated and progresses, and is implicated in the etiology of other conditions that affect cancer risk and prognosis, such as type 2 diabetes, cardiovascular disease, and visceral obesity. Emerging human evidence, primarily epidemiological, suggests that walnuts impact risk of these chronic diseases via inflammation. The published literature documents associations between walnut consumption and reduced risk of cancer, and mortality from cancer, diabetes, and cardiovascular disease, particularly within the context of the Mediterranean Diet.

OBJECTIVE
This paper will explore the translation and application of human evidence regarding connections with cancer and biomarkers of inflammation to the development of dietary guidance for the public and individualized dietary advice. Strategies for encouraging dietary patterns that may reduce cancer risk will be explored.

CONCLUSION
While encouraging, follow-up in human intervention trials is needed to better elucidate any potential cancer prevention effect of walnuts, per se. In humans, the far-reaching positive effects of a plant-based diet that includes walnuts may be the most critical message for the public. Indeed, appropriate translation of nutrition research is essential for facilitating healthful consumer dietary behavior.

PUBLISHED : JULY 28, 2014
STUDY TYPE : SCIENTIFIC MEETING PROCEEDINGS
TOPIC : CANCER
SOURCE : http://e-nrp.org/DOIx.php?id=10.4162/nrp.2014.8.4.347

Walnut Polyphenol Metabolites, Urolithins A And B, Inhibit The Expression Of The Prostate-Specific Antigen And The Androgen Receptor In Prostate Cancer Cells

By Claudia Sánchez-González, Carlos J. Ciudad, Véronique Noé and Maria Izquierdo-Pulido

BACKGROUND
Walnuts have been gathering attention for their health-promoting properties. They are rich in polyphenols, mainly ellagitannins (ETs) that after consumption are hydrolyzed to release ellagic acid (EA). EA is further metabolized by microbiota to form urolithins, such as A and B, which are absorbed. ETs, EA and urolithins have shown to slow the proliferation and growth of different types of cancer cells but the mechanisms remain unclear.

DESIGN
We investigate the role of urolithins in the regulatory mechanisms in prostate cancer, specifically those related to the androgen receptor (AR), which have been linked to the development of this type of cancer.

RESULT
In our study, urolithins down-regulated the mRNA and protein levels of both prostate specific antigen (PSA) and AR in LNCaP cells. The luciferase assay performed with a construct containing three androgen response elements (AREs) showed that urolithins inhibit AR-mediated PSA expression at the transcriptional level. Electrophoretic mobility shift assays revealed that urolithins decreased AR binding to its consensus response element. Additionally, urolithins induced apoptosis in LNCaP cells, and this effect correlated with a decrease in Bcl-2 protein levels.

CONCLUSION
In summary, urolithins attenuate the function of the AR by repressing its expression, causing a down-regulation of PSA levels and inducing apoptosis. Our results suggest that a diet rich in ET-containing foods, such as walnuts, could contribute to the prevention of prostate cancer.

PUBLISHED : AUGUST 19, 2014
STUDY TYPE : IN VITRO STUDY
TOPIC : CANCER
SOURCE : http://pubs.rsc.org/en/content/articlelanding/2014/fo/c4fo00542b#!divAbstract

TRAMP Prostate Tumor Growth Is Slowed By Walnut Diets Through Altered IGF-1 Levels, Energy Pathways, And Cholesterol Metabolism

By Hyunsook Kim, Wallace Yokoyama, Paul A. Davis

BACKGROUND
Dietary changes could potentially reduce prostate cancer morbidity and mortality.

METHOD
Transgenic adenocarcinoma of the mouse prostate (TRAMP) prostate tumor responses to a 100 g of fat/kg diet (whole walnuts, walnut oil, and other oils; balanced for macronutrients, tocopherols [a-and c]) for 18 weeks ad libitum were assessed. TRAMP mice (n = 17 per group) were fed diets with 100 g fat from either whole walnuts (diet group WW), walnut-like fat (diet group WLF, oils blended to match walnut’s fatty acid profile), or as walnut oil (diet group WO, pressed from the same walnuts as WW). Fasted plasma glucose was from tail vein blood, blood was obtained by cardiac puncture, and plasma stored frozen until analysis. Prostate (genitourinary intact [GUI]) was weighed and stored frozen at – 80_C. Plasma triglyceride, lipoprotein cholesterol, plasma multianalyte levels (Myriad RBM Rat Metabolic MAP), prostate (GUI), tissue metabolites (Metabolon, Inc., Durham, NC, USA), and mRNA (by Illumina NGS) were determined.

RESULT
The prostate tumor size, plasma insulin-like growth factor-1 (IGF-1), high density lipoprotein, and total cholesterol all decreased significantly (P< .05) in both WW and WO compared to WLF. Both WW and WO versus WLF showed increased insulin sensitivity (Homeostasis Model Assessment [HOMA]), and tissue metabolomics found reduced glucose-6-phosphate, succinylcarnitine, and 4-hydroxybutyrate in these groups suggesting effects on cellular energy status. Tissue mRNA levels also showed changes suggestive of altered glucose metabolism with WW and WO diet groups having increased PCK1 and CIDEC mRNA expression, known for their roles in gluconeogenesis and increased insulin sensitivity, respectively. WW and WO group tissues also had increased MSMB mRNa a tumor suppressor and decreased COX-2 mRNA, both reported to inhibit prostate tumor growth.

CONCLUSION
Walnuts reduced prostate tumor growth by affecting energy metabolism along with decreased plasma IGF-1 and cholesterol. These effects are not due to the walnut’s N-3 fatty acids, but due to component(s) found in the walnut’s fat component.

PUBLISHED : OCTOBER 29, 2014
STUDY TYPE : ANIMAL FEEDING STUDY
TOPIC : CANCER
SOURCE : http://online.liebertpub.com/doi/abs/10.1089/jmf.2014.0061

Dietary Walnut Suppression Of Colorectal Cancer In Mice: Mediation By MiRNA Patterns And Fatty Acid Incorporation

By Michael A. Tsoukas, Byung-Joon Ko, Theodore R. Witte, Fadime Dincer, W. Elaine Hardman, Christos S. Mantzoros

BACKGROUND
Colorectal cancer, unlike many other malignancies, may be preventable. Recent studies have demonstrated an inverse association between nut consumption and incidence of colon cancer; however, the underlying mechanisms are not fully understood. An emerging concept suggests that microribonucleic acids (miRNAs) may help explain the relationship between walnut consumption and decreased colorectal neoplasia.

METHOD
Seven days after HT-29 colon cancer cell injection, mice were randomized to either control or walnut diets for 25 days of diet treatment. Thirty samples of tumor and of omental adipose were analyzed to determine changes in lipid composition in each dietary group.

RESULT
In the tumors of the walnut-containing diet, we found significant increases in α-linolenic, eicosapentaenoic, docosahexaenoic and total omega-3 acids, and a decrease in arachidonic acid, as compared to the control diet. Final tumor size measured at sacrifice was negatively associated with percentage of total omega-3 fatty acid composition (r=−0.641, P=.001). MicroRNA expression analysis of colorectal tumor tissue revealed decreased expression of miRNAs 1903, 467c and 3068 (P.05) and increased expression of miRNA 297a* (P=.0059) in the walnut-treated group as compared to control diet.

CONCLUSION
Our results indicate that changes in the miRNA expression profiles likely affect target gene transcripts involved in pathways of anti-inflammation, antivascularization, antiproliferation and apoptosis. We also demonstrate the incorporation of protective fatty acids into colonic epithelium of walnut-fed mice, which may independently alter miRNA expression profiles itself. Future studies of the mechanism of widespread miRNA regulation by walnut consumption are needed to offer potential prognostic and therapeutic targets.

*Preliminary animal research has been investigating the potential benefit walnuts may have on a variety of cancers including breast, prostate, and colorectal. Please note, that these animal studies are provided as background and used to formulate hypotheses for additional research needed to determine the effects on humans.

PUBLISHED : APRIL 1, 2015
STUDY TYPE : ANIMAL FEEDING STUDY
TOPIC : HEALTH & WALNUTS, CANCER
SOURCE : http://www.jnutbio.com/article/S0955-2863(15)00070-4/fulltext