BERKELEY, CA (UroToday.com) - We initiated this study on walnuts and prostate cancer because earlier publications had shown that a walnut-enriched diet reduced the growth of human breast cancer cells implanted into immune-compromised nude mice. Walnuts were selected as the supplemental whole food since they contain a variety of cancer fighting ingredients including omega 3-fatty acids (alpha-linolenic acid or ALA in particular), ellagic acid, phytosterols and the antioxidants vitamin E and melatonin, the latter of which also has significant oncostatic activity.
For this investigation, the authors chose LNCaP human prostate cancer cells. These are androgen-sensitive adenocarcinoma cells and were selected because they are well characterized and have often been used in tests designed to identify molecules that have the ability to restrict growth of prostate cancer. 1.5 million rapidly proliferating LNCaP cells, in combination with a small amount of incubation fluid and Matrigel (1:1), were subcutaneously inoculated on the backs of nude mice; Matrigel is an agent that serves as a basement membrane matrix which promotes the growth of the cancer cells. The back was selected as the inoculation site so the growing tumors could easily be visually inspected throughout the study. Some of the inoculated mice had been eating a walnut-enriched diet for roughly 2 weeks before cancer cell inoculation, while the others had received the control AIN-76A diet (see below), which contained no walnut product. Following the inoculation of the cancer cells, the control and walnut diets were fed for the remainder of the study.
Both diets were powdered and carefully crafted. The control diet was equivalent to the American Institute of Nutrition (AIN)-76A diet. The walnut-enriched diet consisted of the basic AIN-76A formulation to which was added powdered fresh walnuts such that 18% of the calories were from walnut. The walnuts were powdered so the mice could not selectively eat this ingredient. Importantly, the amount of walnut consumed by the mice was calculated to be roughly equivalent to a human diet that would include two ounces (about two handfuls) of walnuts daily and would provide 370 calories of a 2 000 calorie/day diet. The control and walnut diets were isocaloric and isonutrient. To prevent any deterioration of the dietary ingredients they were refrigerated after they were prepared and the mice were given fresh diets 3 times per week.
Because the location of the tumors, their growth rate could be easily monitored once they became palpable (when they were about 3 mm diameter); they were measured with a digital calipers in two dimensions 2 or 3 times per week and a standard formula was used to calculate their weight. The dates the tumors first became palpable and their growth rates were recorded.
The first tumors became recognizable 3 to 4 weeks after the prostate cancer cells had been inoculated in mice. However, there was a large difference between the groups in terms of the percentage of animals in which tumors grew. Thus, during the course of the investigation prostate cancers developed in 44% of the control mice while only 19% of the mice eating walnut developed palpable tumors. Also, the growth rate and mean final tumor size were much greater in the control animals than in the walnut-eating mice. At the termination of the study, the mean tumor weight in the control mice was 8 times larger than those of the mice given the walnut diet. In summary, many more tumors developed and they grew much larger in the control diet mice relative to these parameters in the mice consuming the walnut diet.
The strengths of the study include the fact that great care was taken in the preparation of the diets. These were precisely formulated to be isocaloric and isonutrient so the only difference was that one diet contained walnut while the control diet did not. Moreover, the amount of walnut the mice ate daily was compatible with a human diet which would include only 18% of the calories from walnut (about 2 ounces). Thus, if an individual wanted to apply this information for their personal use, it would be an easy dietary adjustment to make. Also, importantly, well characterized and extensively-studied human prostate cancer cells were used in the investigation. Finally, the large differences in the number of prostate cancers that were initiated and their markedly differential growth rates strengthen the significance of the findings. Thus, the walnut diet reduced the initiation of prostate cancer growth and, once the tumors were initiated, their progressive growth was substantially slowed.
A weakness of the findings is that normally when LNCaP cells are inoculated nearly all the animals typically develop tumors in otherwise untreated mice. In the present report, the percentage of control mice that grew tumors was lower than expected; however, the walnut diet obviously further decreased this percentage.
On the basis of the experimental design, we were not able to identify what ingredient in the walnut accounted for the inhibition of prostate tumor growth. Several walnut ingredients mentioned above have been shown to have cancer inhibiting activity. Given the relative amounts of these cancer-fighting ingredients in the walnut, however, we feel that it was the combination of ingredients in walnuts, i.e., the whole food that suppressed prostate tumor growth.
Written by:
Russel J. Reiter, PhD, Dr.h.c.mult. as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Professor of Cell Biology
Editor-in-Chief, Journal of Pineal Research
Department of Cellular and Structural Biology
UT Health Science Center
San Antonio, Texas 78229, USA
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A walnut-enriched diet reduces the growth of LNCaP human prostate cancer xenografts in nude mice - Abstract
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