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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.

Holcombe RF, Martinez M, Planutis K, Planutiene M - Nutr J (2015)

Bottom Line: The expression of CyclinD1 (p < 0 · 01), AXIN2, CD133 (p = 0 · 02) and Ki67 (p = 0 · 002) were all reduced after grape ingestion.Individuals over 50 years of age and those with high dietary arginine consumption had increased basal expression of CyclinD1, AXIN2, cMYC and CD133 (p value range 0 · 04 to <0 · 001) that, following grape ingestion, were reduced to levels seen in younger participants.The reduction in Wnt signaling and mucosal proliferation seen following short-term ingestion of 1/3-1 lb (0.15-0.45 kg) of grapes per day may reduce the risk of mutational events that can facilitate colon carcinogenesis.The potential benefit is most marked for high-risk older individuals and individuals whose diet is high in arginine intake.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology & Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, One Gustav L. Levy Place, Box 1128, New York, NY, 10029, USA. Randall.holcombe@mssm.edu.

ABSTRACT
A diet rich in fruits and vegetables, and a grape-derived compound, resveratrol, have been linked to a reduced incidence of colon cancer. In vitro and in vivo, resveratrol suppresses Wnt signaling, a pathway constitutively activated in over 85 % of colon cancers.Thirty participants were placed on a low resveratrol diet and subsequently allocated to one of three groups ingesting 1/3-to-1 lb (0.15-0.45 kg) of grapes per day for 2 weeks. Dietary information was collected via 24-h recall. Colon biopsies for biomarker analysis were obtained pre- and post-grape and evaluated for the expression of Wnt pathway target genes and for markers of proliferation by RT-PCR and immunohistochemistry.Participants lost an average of 2 · 6 lb (1.2 kg, p = 0 · 0018) during the period of grape ingestion. The expression of CyclinD1 (p < 0 · 01), AXIN2, CD133 (p = 0 · 02) and Ki67 (p = 0 · 002) were all reduced after grape ingestion. Individuals over 50 years of age and those with high dietary arginine consumption had increased basal expression of CyclinD1, AXIN2, cMYC and CD133 (p value range 0 · 04 to <0 · 001) that, following grape ingestion, were reduced to levels seen in younger participants.The reduction in Wnt signaling and mucosal proliferation seen following short-term ingestion of 1/3-1 lb (0.15-0.45 kg) of grapes per day may reduce the risk of mutational events that can facilitate colon carcinogenesis. The potential benefit is most marked for high-risk older individuals and individuals whose diet is high in arginine intake. Dietary grape supplementation may play a role in colon cancer prevention for high-risk individuals.

No MeSH data available.


Related in: MedlinePlus

Change in individual (a) and mean (b) weights for the 30 participants from pre-grape ingestion timepoint to the post-grape ingestion timepoint. Grape ingestion significantly reduced expression as measured by qRT-PCR of CyclinD1 (c) and CD133 (e) with a non-statistically significant reduction in AXIN2 (d). However, CyclinD1 and AXIN2 levels in colonic mucosa were strongly correlated with each other both pre-grape ingestion (h) and post-grape ingestion (i). Ki67 expression was also reduced following grape ingestion (f). This was measured by calculating the percentage of positively staining cells in the lower 1/3 of colonic crypts (g; representative photomicrograph—green represents positive immunofluorescence). *p < 0 · 05; ** p < 0 · 01; *** p < 0 · 005
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Fig2: Change in individual (a) and mean (b) weights for the 30 participants from pre-grape ingestion timepoint to the post-grape ingestion timepoint. Grape ingestion significantly reduced expression as measured by qRT-PCR of CyclinD1 (c) and CD133 (e) with a non-statistically significant reduction in AXIN2 (d). However, CyclinD1 and AXIN2 levels in colonic mucosa were strongly correlated with each other both pre-grape ingestion (h) and post-grape ingestion (i). Ki67 expression was also reduced following grape ingestion (f). This was measured by calculating the percentage of positively staining cells in the lower 1/3 of colonic crypts (g; representative photomicrograph—green represents positive immunofluorescence). *p < 0 · 05; ** p < 0 · 01; *** p < 0 · 005

Mentions: During the two weeks of grape consumption, participants lost an average of 2 · 6 lbs (1 · 2 Kg; p = 0 · 0018; Fig. 2) despite significant increases in total carbohydrates, percent of calories from carbohydrates and total sugars (Table 2). Overall KCALS were unchanged. Participants reported that they often felt “full”, particularly those consuming 1 lb (0.45 kg) of grapes per day, and subjectively reported that they snacked less because of this. Interestingly, there was a significant reduction in the percentage of calories from fat (35 · 32 to 30 · 77 %) while ingesting grapes (p = 0 · 011; Table 2). Other significant changes included an increase in copper, potassium and vitamin B6 and a decrease in Biochanin A ingestion.Fig. 2


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.

Holcombe RF, Martinez M, Planutis K, Planutiene M - Nutr J (2015)

Change in individual (a) and mean (b) weights for the 30 participants from pre-grape ingestion timepoint to the post-grape ingestion timepoint. Grape ingestion significantly reduced expression as measured by qRT-PCR of CyclinD1 (c) and CD133 (e) with a non-statistically significant reduction in AXIN2 (d). However, CyclinD1 and AXIN2 levels in colonic mucosa were strongly correlated with each other both pre-grape ingestion (h) and post-grape ingestion (i). Ki67 expression was also reduced following grape ingestion (f). This was measured by calculating the percentage of positively staining cells in the lower 1/3 of colonic crypts (g; representative photomicrograph—green represents positive immunofluorescence). *p < 0 · 05; ** p < 0 · 01; *** p < 0 · 005
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4472174&req=5

Fig2: Change in individual (a) and mean (b) weights for the 30 participants from pre-grape ingestion timepoint to the post-grape ingestion timepoint. Grape ingestion significantly reduced expression as measured by qRT-PCR of CyclinD1 (c) and CD133 (e) with a non-statistically significant reduction in AXIN2 (d). However, CyclinD1 and AXIN2 levels in colonic mucosa were strongly correlated with each other both pre-grape ingestion (h) and post-grape ingestion (i). Ki67 expression was also reduced following grape ingestion (f). This was measured by calculating the percentage of positively staining cells in the lower 1/3 of colonic crypts (g; representative photomicrograph—green represents positive immunofluorescence). *p < 0 · 05; ** p < 0 · 01; *** p < 0 · 005
Mentions: During the two weeks of grape consumption, participants lost an average of 2 · 6 lbs (1 · 2 Kg; p = 0 · 0018; Fig. 2) despite significant increases in total carbohydrates, percent of calories from carbohydrates and total sugars (Table 2). Overall KCALS were unchanged. Participants reported that they often felt “full”, particularly those consuming 1 lb (0.45 kg) of grapes per day, and subjectively reported that they snacked less because of this. Interestingly, there was a significant reduction in the percentage of calories from fat (35 · 32 to 30 · 77 %) while ingesting grapes (p = 0 · 011; Table 2). Other significant changes included an increase in copper, potassium and vitamin B6 and a decrease in Biochanin A ingestion.Fig. 2

Bottom Line: The expression of CyclinD1 (p < 0 · 01), AXIN2, CD133 (p = 0 · 02) and Ki67 (p = 0 · 002) were all reduced after grape ingestion.Individuals over 50 years of age and those with high dietary arginine consumption had increased basal expression of CyclinD1, AXIN2, cMYC and CD133 (p value range 0 · 04 to <0 · 001) that, following grape ingestion, were reduced to levels seen in younger participants.The reduction in Wnt signaling and mucosal proliferation seen following short-term ingestion of 1/3-1 lb (0.15-0.45 kg) of grapes per day may reduce the risk of mutational events that can facilitate colon carcinogenesis.The potential benefit is most marked for high-risk older individuals and individuals whose diet is high in arginine intake.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology & Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, One Gustav L. Levy Place, Box 1128, New York, NY, 10029, USA. Randall.holcombe@mssm.edu.

ABSTRACT
A diet rich in fruits and vegetables, and a grape-derived compound, resveratrol, have been linked to a reduced incidence of colon cancer. In vitro and in vivo, resveratrol suppresses Wnt signaling, a pathway constitutively activated in over 85 % of colon cancers.Thirty participants were placed on a low resveratrol diet and subsequently allocated to one of three groups ingesting 1/3-to-1 lb (0.15-0.45 kg) of grapes per day for 2 weeks. Dietary information was collected via 24-h recall. Colon biopsies for biomarker analysis were obtained pre- and post-grape and evaluated for the expression of Wnt pathway target genes and for markers of proliferation by RT-PCR and immunohistochemistry.Participants lost an average of 2 · 6 lb (1.2 kg, p = 0 · 0018) during the period of grape ingestion. The expression of CyclinD1 (p < 0 · 01), AXIN2, CD133 (p = 0 · 02) and Ki67 (p = 0 · 002) were all reduced after grape ingestion. Individuals over 50 years of age and those with high dietary arginine consumption had increased basal expression of CyclinD1, AXIN2, cMYC and CD133 (p value range 0 · 04 to <0 · 001) that, following grape ingestion, were reduced to levels seen in younger participants.The reduction in Wnt signaling and mucosal proliferation seen following short-term ingestion of 1/3-1 lb (0.15-0.45 kg) of grapes per day may reduce the risk of mutational events that can facilitate colon carcinogenesis. The potential benefit is most marked for high-risk older individuals and individuals whose diet is high in arginine intake. Dietary grape supplementation may play a role in colon cancer prevention for high-risk individuals.

No MeSH data available.


Related in: MedlinePlus