No abstract

Walnuts contain components that may slow cancer growth including omega 3 fatty acids, phytosterols, polyphenols, carotenoids, and melatonin. A pilot study was performed to determine whether consumption of walnuts could affect growth of MDA-MB 231 human breast cancers implanted into nude mice. Tumor cells were injected into nude mice that were consuming an AIN-76A diet slightly modified to contain 10% corn oil. After the tumors reached 3 to 5 mm diameter, the diet of one group of mice was changed to include ground walnuts, equivalent to 56 g (2 oz) per day in humans. The tumor growth rate from Day 10, when tumor sizes began to diverge, until the end of the study of the group that consumed walnuts (2.9 +/- 1.1 mm(3)/day; mean +/- standard error of the mean) was significantly less (P > 0.05, t-test of the growth rates) than that of the group that did not consume walnuts (14.6 +/- 1.3 mm(3)/day). The eicosapentaenoic and docosahexaenoic acid fractions of the livers of the group that consumed walnuts were significantly higher than that of the group that did not consume walnuts. Tumor cell proliferation was decreased, but apoptosis was not altered due to walnut consumption. Further work is merited to investigate applications to cancer in humans.

The fermented wheat germ extract (code name: MSC, trade name: Avemar), with standardized benzoquinone content has been shown to inhibit tumor propagation and metastases formation in vivo. The aim of this study was to understand the molecular and cellular mechanisms of the anti-tumor effect of MSC. Therefore, we have designed in vitro model experiments using T and B tumor lymphocytic cell lines. Tyrosine phosphorylation of intracellular proteins and elevation of the intracellular Ca 2+ concentration were examined using immunoblotting with anti-phosphotyrosine antibody and cytofluorimetry by means of Ca 2+ sensitive fluorescence dyes, Fluo-3AM and FuraRed-AM, respectively. Apoptosis was measured with cytofluorimetry by staining the DNA with propidium iodide and detecting the 'sub-G 1 ' cell population. The level of the cell surface MHC class I molecules was analysed with indirect immunofluorescence on cytofluorimeter using a monoclonal antibody to the non-polymorphic region of the human MHC class I. MSC stimulated tyrosine phosphorylation of intracellular proteins and the influx of extracellular Ca 2+ resulted in elevation of intracellular Ca 2+ concentration. Prominent apoptosis of 20-40% was detected upon 24 h of MSC treatment of the cell lines. As a result of the MSC treatment, the amount of the cell surface MHC class I proteins was downregulated by 70-85% compared to the non-stimulated control. MSC did not induce a similar degree of apoptosis in healthy peripheral blood mononuclear cells. Inhibition of the cellular tyrosine phosphatase activity or Ca 2+ influx resulted in the opposite effect increasing or diminishing the Avemar induced apoptosis as well as the MHC class I downregulation, respectively. A benzoquinone component (2,6-dimethoxi-pbenzoquinone) in MSC induced similar apoptosis and downregulation of the MHC class I molecules in the tumor T and B cell lines to that of MSC. These results suggest that MSC acts on lymphoid tumor cells by reducing MHC class I expression and selectively promoting apoptosis of tumor cells on a tyrosine phosphorylation and Ca 2+ influx dependent way. One of the components in MSC, 2,6-dimethoxi-pbenzoquinone was shown to be an important factor in MSC mediated cell response.

No 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.

Prostate cancer incidence and mortality are high in the Western world and high ω-6/ω-3 PUFA in the Western diet may be a contributing factor. We investigated whether changing from a diet that approximates ω-6 fat content of the Western diet to a high ω-3 fat diet at adulthood might reduce prostate cancer risk. Female SV 129 mice that had consumed a high ω-6 diet containing corn oil for 2 weeks were bred with homozygous C3(1)Tag transgenic male mice. All male offspring were weaned to the corn oil diet (CO) until postpuberty when half of the male offspring were transferred to a high ω-3 diet containing canola oil and fish oil concentrate (FS). High ω-3 diet increased ω-3 and decreased ω-6 fat content of mice tissues. Average weights of prostate and genitourinary bloc were significantly lower in mice consuming high ω-3 diet at adulthood (CO-FS) than mice fed a lifetime high ω-6 diet (CO–CO). There was slower progression of tumorigenesis in dorsalateral prostate of CO-FS than in CO–CO mice. CO-FS mice had slightly lower plasma testosterone level at 24 and 40 weeks, significantly lower estradiol level at 40 weeks and significantly less expressed androgen receptor (AR) in the dorsalateral prostate at 40 weeks than CO–CO mice. Consumption of high ω-3 diet lowered the expression of genes expected to increase proliferation and decrease apoptosis in dorsalateral prostate. Our results suggest that consumption of high ω-3 diet slows down prostate tumorigenesis by lowering estradiol, testosterone and AR levels, promoting apoptosis and suppressing cell proliferation in C3(1)Tag mice.

Galectin-1 is a member of the family of β-galactoside binding animal lectins, galectins. Its presence in the bone marrow has been detected; however, its role in the regulation of hematopoiesis is unknown. In the present study, we have evaluated the effect of recombinant human galectin-1 on the proliferation and survival of murine and human hematopoietic stem and progenitor cells. We show that low amount of galectin-1 (10 ng/ml) increases the formation of granulocyte-macrophage and erythroid colonies and the frequencies of day-7 cobblestone area-forming cells on a lactose-inhibitable fashion. In contrast, high amount of galectin-1 (10 μg/ml) dramatically reduces the growth of the committed blood-forming progenitor cells as well as the much younger, lineage-negative hematopoietic cells (day-28 to -35 cobblestone area-forming cells). This inhibition is not blocked by lactose and, therefore, is largely independent of the β-galactoside-binding site of the lectin. Furthermore, assays to detect apoptosis render it likely that the high amount of galectin-1 acts as a classical proapoptotic factor for the premature hematopoietic cells.

No abstract