Dietary Walnut Suppressed Mammary Gland Tumorigenesis in the C(3)1 TAg Mouse W. Elaine Hardmana, Gabriela Iona, Juliana A. Akinsetea & Theodore R. Wittea
Abstract Walnuts contain multiple ingredients that, individually, have been shown to slow cancer growth, including omega-3 fatty acids, antioxidants, and phytosterols. In previous research, consumption of walnuts has slowed the growth of implanted breast cancers. We wanted to determine whether regular walnut consumption might reduce the risk for developing cancer. Homozygous male C(3)1 TAg mice were bred with female SV129 mice consuming either the control AIN-76 diet or the walnut-containing diet. At weaning, the female hemizygous pups were randomized to control or walnut-containing diets and followed for tumor development. Compared to a diet without walnuts, consumption of walnuts significantly reduced tumor incidence (fraction of mice with at least one tumor), multiplicity (number of glands with tumor/mouse), and size. Gene expression analyses indicated that consumption of the walnut diet altered expression of multiple genes associated with proliferation and differentiation of mammary epithelial cells. A comparison with another dietary intervention indicated that the omega 3 content alone did not account for the extent of tumor suppression due to the walnut. The results of this study indicate that walnut consumption could contribute to a healthy diet to reduce risk for breast cancer.
Conclusion These data indicate that exposure to a small amount of walnut in the diet of this transgenic mouse slowed the development and reduced the multiplicity of mammary gland cancers but does not define the mechanism of action for the walnut nor an active ingredient of the walnut. Walnut in the diet was associated with alterations in cell signaling pathways involved in proliferation, cell differentiation, and apoptosis. The signaling pathways altered in mammary glands of these mice have been identified as important in the development of human breast cancer, thus this study should be relevant to humans. The fatty acid composition of the mammary glands was altered but comparison to another study with the same amount of omega 3 fatty acids in the diet indicates that increased omega 3 fatty acids in the mammary gland does not explain the altered tumor incidence. However, alterations in dietary gamma tocopherol were inversely associated with tumorigenesis.More work will need to be done to determine the components of walnut and the mechanisms associated with tumor suppression. However, humans eat the whole nut, not specific components. It seems likely that incorporation of walnuts as part of a healthy diet could reduce the risk for breast cancer in humans.
Validation of the Antiproliferative Effects of Organic Extracts from the Green Husk of Juglans regia L. on PC-3 Human Prostate Cancer Cells by Assessment of Apoptosis-Related Genes Ali A. Alshatwi,* Tarique N. Hasan, Gowhar Shafi, Naveed Ahmed Syed, Abdullah H. Al-Assaf, Mohammed S. Alamri, and Abdrohman S. Al-Khalifa
Abstract With the increased use of plant-based cancer chemotherapy, exploring the antiproliferative effects of phytochemicals for anticancer drug design has gained considerable attention worldwide. This study was undertaken to investigate the effect of walnut green husk extracts on cell proliferation and to determine the possible molecular mechanism of extract-induced cell death by quantifying the expression of Bcl-2, Bax, caspases-3, and Tp53. PC-3 human prostate cancer cells. In this study, we found that green husk extracts suppressed proliferation and induced apoptosis in a dose- and time-dependent manner by modulating expression of apoptosis-related genes. This involved DNA fragmentation (determined by TUNEL assay) and significant changes in levels of mRNA and the expression of corresponding proteins. An increase in expressions of Bax, caspase-3, and tp53 genes and their corresponding proteins was detected using real-time PCR and western blot analysis in PC-3 cells treated with the green husk organic extracts. In contrast, Bcl2 expression was downregulated after exposure to the extracts. Our data suggest the presence of bioactive compound(s) in walnut green husks that are capable of killing prostate carcinoma cells by inducing apoptosis and that the husks are a candidate source of anticancer drugs.
Source : Evid Based Complement Alternat Med. 2012; 2012: 103026. doi: 10.1155/2012/103026 Link to Full Article
The effect of walnut intake on factors related to prostate and vascular health in older men
Background Tocopherols may protect against prostate cancer and cardiovascular disease (CVD).
Methods We assessed the effect of walnuts, which are rich in tocopherols, on markers of prostate and vascular health in men at risk for prostate cancer. We conducted an 8-week walnut supplement study to examine effects of walnuts on serum tocopherols and prostate specific antigen (PSA). Subjects (n = 21) consumed (in random order) their usual diet +/- a walnut supplement (75 g/d) that was isocalorically incorporated in their habitual diets. Prior to the supplement study, 5 fasted subjects participated in an acute timecourse experiment and had blood taken at baseline and 1, 2, 4, and 8 h after consuming walnuts (75 g).
Results During the timecourse experiment, triglycerides peaked at 4 h, and gamma-tocopherol (γ-T) increased from 4 to 8 h. Triglyceride – normalized γ-T was two-fold higher (P = 0.01) after 8 versus 4 h. In the supplement study, change from baseline was +0.83 ± 0.52 μmol/L for γ-T, -2.65 ± 1.30 μmol/L for alpha-tocopherol (α-T) and -3.49 ± 1.99 for the tocopherol ratio (α-T: γ-T). A linear mixed model showed that, although PSA did not change, the ratio of free PSA:total PSA increased and approached significance (P = 0.07). The α-T: γ-T ratio decreased significantly (P = 0.01), partly reflecting an increase in serum γ-T, which approached significance (P = 0.08).
Conclusion The significant decrease in the α-T: γ-T ratio with an increase in serum γ-T and a trend towards an increase in the ratio of free PSA:total PSA following the 8-week supplement study suggest that walnuts may improve biomarkers of prostate and vascular status.