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Transgenic alfalfa that accumulates piceid (trans-resveratrol-3-O-beta-D-glucopyranoside) requires the presence of beta-glucosidase to inhibit the formation of aberrant crypt foci in the colon of CF-1 mice.

Abstract
Plants have been genetically enhanced to produce a number of products for agricultural, industrial and pharmaceutical purposes. This technology could potentially be applied to providing chemoprevention strategies to the general population. Resveratrol (3,5,4'-trihydroxystilbene) is a compound that has been shown to have protective activity against a number of cancers and could be an ideal candidate for such an application. Alfalfa that was genetically modified to express resveratrol-synthase was used as a model in applying biotechnological approaches to cancer prevention. The transgenic alfalfa, which accumulates resveratrol as a glucoside (piceid = trans-resveratrol-3-O-Beta-D-glucopyranoside) (152 +/- 17.5 microg piceid/g dry weight), was incorporated into a standard mouse diet at 20% of the diet by weight and fed for 5 wk to 6-wk-old, female CF-1 mice (N = 17-30) that were injected with a single dose of azoxymethane (5 mg/kg body weight). While the addition of resveratrol-aglycone (20 mg/kg diet) to the basal diet reduced the number of aberrant crypt foci/mouse, the transgenic alfalfa did not inhibit the number, size, or multiplicity of aberrant crypt foci in the colon of the CF-1 mice relative to control alfalfa which does not accumulate resveratrol-glucoside. However, diets containing transgenic alfalfa with an exogenous Beta-glucosidase (860 U/kg diet) did significantly inhibit the number of aberrant crypt foci in the distal 2 cm of the colon of the mice relative to mice fed diets containing the transgenic alfalfa without the enzyme (P < 0.05; Fisher's Combination of p-values). The Beta-glucosidase alone appeared to have no effect on the inhibition of aberrant crypt foci. These results suggest that piceid in transgenic piceid-accumulating alfalfa was not bioavailable.
AuthorsBrian D Kineman, Angela Au, Nancy L Paiva, Mark S Kaiser, E Charles Brummer, Diane F Birt
JournalNutrition and cancer (Nutr Cancer) Vol. 58 Issue 1 Pg. 66-74 ( 2007) ISSN: 0163-5581 [Print] United States
PMID17571969 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Glucosides
  • Stilbenes
  • Acyltransferases
  • resveratrol synthase
  • beta-Glucosidase
  • Resveratrol
  • polydatin
Topics
  • Acyltransferases (metabolism)
  • Animals
  • Colonic Neoplasms (chemically induced, pathology, prevention & control)
  • Disease Models, Animal
  • Female
  • Glucosides (metabolism, pharmacology)
  • Humans
  • Medicago sativa (genetics)
  • Mice
  • Mice, Inbred Strains
  • Plants, Genetically Modified
  • Precancerous Conditions
  • Random Allocation
  • Resveratrol
  • Stilbenes (metabolism, pharmacology)
  • beta-Glucosidase (metabolism, pharmacology)

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