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Research Area: Cancer

The effect of nut consumption on cancer is a relatively new area of research. Tree nuts contain a wide range of nutrients with recognized benefits to human health including unsaturated fats, protein, vitamins (i.e., vitamin E, folate and niacin), minerals (i.e., magnesium, calcium and potassium) and phytochemicals—all of which may offer anticarcinogenic, anti-inflammatory and antioxidant properties.

In a recent study, researchers concluded that there was an inverse association of dietary nut consumption with cancer risk, especially for cancers of the digestive system[i].  A number of studies have been conducted to date looking at the effect of nuts on colorectal cancer, which affects both men and women, and is the second leading cause of cancer-related deaths in the United States and third most common cancer worldwide. In one study, researchers found an association between high frequency of nut consumption and reduced risk of colorectal cancer[ii]. In another study[iii], colon cancer patients who consumed nuts had a significant decrease in cancer recurrence and death.

While nut consumption is associated with reduced total and certain cause-specific mortality in general populations, its association with cancer outcomes among long-term breast cancer survivors remains unknown. Researchers in one study[IV] examined the associations of nut consumption (including tree nuts and peanuts) at 5-years postdiagnosis, with overall survival and disease-free survival among 3,449 long-term breast cancer survivors from the Shanghai Breast Cancer Survival Study. The data showed that nut consumption was associated with better survival, particularly disease-free survival, among long-term breast cancer survivors.

At Harvard, researchers looked at the association between nut consumption and prostate cancer risk and mortality among 47,299 men. While nut consumption was not associated with a reduced risk of prostate cancer, men who had prostate cancer and consumed tree nuts five or more times per week after diagnosis, had a significant 34 percent lower risk of overall mortality than those who consumed nuts less than once per month[iv].

While more research on tree nuts and cancer is needed, the research that has been done to date is very promising.

[i]Long, J., Z. Ji, P. Yuan, T. Long, K. Liu, J. Li, L. Cheng, 2020. Nut consumption and risk of cancer: A meta-analysis of prospective studies. Cancer Epidemiol Biomarkers Prev. 29(3):565-573.

[ii] Lee, J., A. Shin, J.H. Oh, J. Kim, 2018. The relationship between nut intake and risk of colorectal cancer: a case control study. Nutrition Journal. 17:37 https://doi.org/10.1186/s12937-018-0345-y.

[iii] Fadelu, T., S. Zhang, D. Niedzwiecki, X. Ye, L.B. Saltz, R.J. Mayer, R.B. Mowat, R. Whittom, A. Hantel, A.B. Benson, D.M. Atienza, M. Messino, H.L. Kindler, A. Venook, S. Ogino, K. Ng, K. Wu, W. Willett, E. Giovannucci, J. Meyerhardt, Y. Bao, C.S. Fuchs, 2018. Nut consumption and survival in patients with stage III colon cancer: results from CALGB 89803 (Alliance). J Clin Oncol. 36(11):1112-1120.

[iv] Cong, W., K. Gu, F. Wang, H. Cai, W. Zheng, P. Bao, X.-O. Shu, 2022. Nut consumption in association with overall mortality and recurrence/disease-specific mortality among long-term breast cancer survivors. International Journal of Cancer.doi.org/10.1002/ijc.33824.

[v]Wang, W., M. Yang, S.A. Kenfield, F.B. Hu, M.J. Stampfer, W.C. Willett, C.S. Fuchs, E.L. Giovannucci, Y. Bao, 2016. Nut consumption and prostate cancer risk and mortality. Br J Cancer. 115(3):371-374.

Walnut phenolic extract and its bioactive compounds suppress colon cancer cell growth by regulating colon cancer stemness.

Lee, J., Y.S. Kim, J. Lee, S.C. Heo, K.L. Lee, S.W. Choi, Y. Kim, 2016. Walnut phenolic extract and its bioactive compounds suppress colon cancer cell growth by regulating colon cancer stemness.Nutrients. 8, 439; doi:10.3390/nu8070439.

Abstract: Walnut has been known for its health benefits, including anti-cardiovascular disease and anti-oxidative properties. However, there is limited evidence elucidating its effects on cancer stem cells (CSCs) which represent a small subset of cancer cells that provide resistance against chemotherapy. This study aimed to evaluate the anti-CSCs potential of walnut phenolic extract (WPE) and its bioactive compounds, including (+)-catechin, chlorogenic acid, ellagic acid, and gallic acid. In the present study, CD133+CD44+ cells were isolated from HCT116 cells using fluorescence-activated cell sorting (FACS) and then treated with WPE. As a result, survival of the CD133+CD44+ HCT116 cells was inhibited and cell differentiation was induced by WPE. In addition, WPE down-regulated the CSC markers, CD133, CD44, DLK1, and Notch1, as well as the β-catenin/p-GSK3β signaling pathway. WPE suppressed the self-renewal capacity of CSCs. Furthermore, the WPE exhibited stronger anti-CSC effects than its individual bioactive compounds. Finally, the WPE inhibited specific CSC markers in primary colon cancer cells isolated from primary colon tumor. These results suggest that WPE can suppress colon cancer by regulating the characteristics of colon CSCs.

 

Compositional analysis of walnut lipid extracts and properties as an anti-cancer stem cell regulator via suppression of the self-renewal capacity.

Chung J, Kim YS, Lee J,  Le JH, Choi SW, Kim Y., 2016. Compositional analysis of walnut lipid extracts and properties as an anti-cancer stem cell regulator via suppression of the self-renewal capacity.Food Sci. Biotechnol. 25(2): 623-629.

Colon cancer is a leading cause of cancer-related deaths worldwide. Effects of walnut (Juglans regia L.) lipid extracts (WLEs) on the self-renewal capacity of cancer stem cells (CSCs) in colon cancer were investigated. The dominant component of WLEs was α-linoleic acid (64.6%), followed by α-linolenic acid (14.6%), and oleic acid (12.6%). A higher concentration of γ-tocopherol (37.1%) was also present than of α-tocopherol (0.6%). CD133+CD44+CSCs treated with WLEs showed inhibition of colony formation and sphere formation, indicating a decrease in the self-renewal capacity. Treatment with WLEs also resulted in down-regulation of protein levels, including Notch1, phospho-GSK3β (p- GSK3β), and β-catenin, which are associated with CSCs and the self-renewing capacity. WLEs rich in essential fatty acids and γ-tocopherol can exert therapeutic actions on colon cancer via targeting of CSCs.

Urolithin A causes p21 up-regulation in prostate cancer cells.

Sánchez-González, C., C.J. Ciudad, M. Izquierdo-Pulido, V. Noé V., 2016. Urolithin A causes p21 up-regulation in prostate cancer cells. Eur J Nutr. 55(3):1099-112.

Purpose: Walnuts contain several bioactive compounds, including pedunculagin, a polyphenol metabolized by microbiota to form urolithins, namely urolithin A (UA). The aim of this study was to determine gene expression changes in prostate cancer cells after incubation with UA. Methods: We performed a genomic analysis to study the effect of UA on LNCaP prostate cells. Cells were incubated with 40 µM UA for 24 h, and RNA was extracted and hybridized to Affymetrix Human Genome U219 array. Microarray results were analyzed using GeneSpring v13 software. Differentially expressed genes (p < 0.05, fold change > 2) were used to perform biological association networks. Cell cycle was analyzed by flow cytometry and apoptosis measured by the rhodamine method and by caspases 3 and 7 activation. Cell viability was determined by MTT assay. Results: We identified two nodes, FN-1 and CDKN1A, among the differentially expressed genes upon UA treatment. CDKN1A was validated, its mRNA and protein levels were significantly up-regulated, and the promoter activation measured by luciferase. Cell cycle analysis showed an increase in G1-phase, and we also observed an induction of apoptosis and caspases 3 and 7 activation upon UA treatment. Conclusion: Our results indicate a potential role of UA as a chemopreventive agent for prostate cancer.

 

Nut consumption and prostate cancer risk and mortality.

Wand, W., M. Yang, S.A. Kenfield, F.B. Hu, M.J. Stampfer, W.C. Willett, C.S. Fuchs, E.L. Giovannucci,  Y. Bao, 2016. Nut consumption and prostate cancer risk and mortality. British Journal of Cancer.doi:10.1038/bjc.2016.181

Background: Little is known of the association between nut consumption, and prostate cancer (PCa) incidence and survivorship. Methods: We conducted an incidence analysis and a case-only survival analysis in the Health Professionals Follow-up Study on the associations of nut consumption (updated every 4 years) with PCa diagnosis, and PCa-specific and overall mortality. Results: In 26 years, 6810 incident PCa cases were identified from 47 299 men. There was no association between nut consumption and being diagnosed with PCa or PCa-specific mortality. However, patients who consumed nuts five or more times per week after diagnosis had a significant 34% lower rate of overall mortality than those who consumed nuts less than once per month (HR=0.66, 95% CI: 0.52–0.83, P-trend=0.0005). Conclusions: There were no statistically significant associations between nut consumption, and PCa incidence or PCa-specific mortality. Frequent nut consumption after diagnosis was associated with significantly reduced overall mortality.