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.
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.
Kineman
Brian D
BD
Department of Food Science and Human Nutrition, Iowa State University, Ames, IA 50011, USA.
Au
Angela
A
Paiva
Nancy L
NL
Kaiser
Mark S
MS
Brummer
E Charles
EC
Birt
Diane F
DF
D000217:Acyltransferases / Q000378:metabolism; D000818:Animals; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D005260:Female; D005960:Glucosides / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D000455:Medicago sativa / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D030821:Plants, Genetically Modified; D011230:Precancerous Conditions; D011897:Random Allocation; D000077185:Resveratrol; D013267:Stilbenes / Q000378:metabolism / Q000494:pharmacology*; D001617:beta-Glucosidase / Q000378:metabolism* / Q000494:pharmacology*
D005960:Glucosides; D013267:Stilbenes; D000217:Acyltransferases; C055200:resveratrol synthase; D001617:beta-Glucosidase; D000077185:Resveratrol; C058229:polydatin