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- Grapes (Vitis vinifera, Vitaceae)
- Colorectal Cancer
- Wnt Signaling
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Date:
02-15-2016 | HC# 081522-538
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Re: Daily Grape Consumption Decreases Gene Expression Associated with Cell Signaling and Proliferation in Colon Cells of Healthy, Adult Subjects
Holcombe
RF, Martinez M, Planutis K, Planutiene M. Effects of a grape-supplemented diet on proliferation and Wnt signaling
in the colonic mucosa are greatest for those over age 50 and with high arginine
consumption. Nutr J. June
2015;14:62. doi: 10.1186/s12937-015-0050-z.
Numerous studies have shown that the risk of
developing colorectal cancer (CRC) decreases with increased consumption of
fruits and vegetables. Grapes (Vitis vinifera,
Vitaceae) contain resveratrol, which has been shown to alter cellular gene
expression. In particular, resveratrol has been shown to suppress Wnt signaling
in colon cancer cells and inhibit intestinal tumor cell growth in several cell and
animal models. Studies in healthy, human subjects also have shown that Wnt
signaling is downregulated with resveratrol intake. However, there is some
debate over the bioavailability of resveratrol in grapes and the effect of
grapes on biomarkers of CRC. The goal of this randomized study was to measure
the effect of daily grape intake on Wnt signaling and Ki67 protein
concentration in colonic mucosa.
Thirty nondiabetic, healthy subjects were enrolled
in this 4-week study at the University of California, Irvine. Subjects were
randomly divided into 1 of 3 groups who consumed either ⅓ lb, ⅔ lb, or 1 lb (0.15
kg, 0.30 kg, or 0.45 kg, respectively) of grapes per day. Subjects were given a
digital kitchen scale and a voucher redeemable at a local grocery store for
red, seedless grapes. For the first 2 weeks of the study, subjects were placed
on a low-resveratrol diet and consumed no grapes. During the second 2 weeks of
the study, subjects consumed the daily allocation of grapes. Subjects recorded
their daily food intake for 24 hours for 3 days during each of the 2-week
periods. Sigmoidoscopies and rectal mucosal biopsies were conducted on day 15
and day 30. Quantitative real-time polymerase chain reaction (PCR) analyses
were performed on the biopsies to measure changes in messenger RNA (mRNA)
expression associated with cell proliferation and Wnt signaling. Markers included
cyclin D1, AXIN2, cMYC, and CD133. The percentage of cells expressing the
proliferation protein, Ki67, also was measured in the biopsies. Data were
analyzed with 1-way analysis of variance, Wilcoxon matched-pairs signed-rank
tests, unpaired t-tests, and linear regression.
The average age of the subjects was 43.28 ±
2.28. Nine men and 21 women completed the study. No differences were found
among the groups in the parameters measured, so data from the groups were analyzed
together. Most subjects lost weight during the grape consumption phase of the
study, and this weight loss was significant (P < 0.005). Cyclin D1, CD133
expression, and Ki67 levels decreased significantly in the biopsies pre-grape
to post-grape (P < 0.01, P = 0.02, and P < 0.005, respectively). This
change in expression was completely dependent on age. Subjects under the age of
50 had no significant change in these markers, whereas subjects over the age of
50 had large, significant decreases. Data were also analyzed by arginine
consumption level because higher arginine intake has been associated with an
increased risk of developing CRC. Twenty-one subjects had arginine intake
levels below the average of 4-5 g/d, whereas 9 subjects had arginine intake
levels above average. In the pre-grape phase of the study, cyclin D1, AXIN2, cMYC,
and CD133 were all significantly higher in subjects with above average arginine
intake (P < 0.05, P < 0.01, P < 0.005, and P < 0.05, respectively).
In addition, there was a large decrease in cyclin D1 with grape consumption in
subjects with high arginine intake.
Daily grape consumption resulted in decreased
gene expression associated with Wnt signaling and cell proliferation in colonic
mucosa cells. The effects of grape consumption were found to be most profound
in older subjects. In other studies, older subjects have been found to have
increased colorectal inflammation and a decreased regenerative capacity of the
colonic mucosa than younger subjects. These changes with age may be related to
the increased incidence of CRC in individuals over the age of 50. The authors
hypothesize that grape consumption may help reduce the risk of CRC in older
individuals. Expression of cell proliferation was also significantly higher in
subjects who had a higher than average arginine intake, and grape consumption
helped reduce the expression of cyclin D1. No relationship was found between
the amount of grapes consumed daily and signaling and proliferation markers.
This may have been due to the very small sample size in each group.
—Cheryl McCutchan, PhD
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