Chemoprevention by Grape Seed Extract and Genistein in Carcinogen-induced Mammary Cancer in Rats Is Diet Dependent

Author: Kim H, Hall P, Smith M, Kirk M, Prasain JK, Barnes S, Grubbs C
Publication: J. of Nutr. 2004 Dec;134(12):3445S-52S

Supplements with natural antioxidants such as proanthocyanidins (grape skin), resveratrol (grape skin), catechins (tea) and isoflavones (soy) are often used because people believe that they can reduce the risk for cancer. Epidemiological studies show that certain Phytochemicals, such as isoflavones and polyphenols, influence cancer risk.

Proanthocyanidins, which are oligomers of catechins, are found and in grape seeds and are used to make grape seed extract. These grape seeds are a waste product of the wine production. Evidence suggests that these proanthocyanidins can be broken down into catechins during metabolism.

The purpose of this study was to investigate if grape seed extract could protect rats against the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) and if the effect of grape seed extract was influences by the diet. Previous studies with grape seed extract and isoflavones did not take consideration on the influence of the diet.

The grape seed extract did not give any protective activity against DMBA-induced breast cancer when feeding the rats with the AIN-76A diet, but there was a 50% reduction in tumor multiplicity when the grape seed extract with given with Teklad (4% fat) rodent diet. Both the AIN-76A diet and Teklad 4% rodent diet are standardized diets used for experiments with rats. Both diets have same overall nutritional content but they differ in the type of protein. The AIN-76A diet uses milk casein and the Teklad diet uses soy, wheat and barley as protein source.

Similar results were observed with the isoflavone genistein. Genistein showed 44% (0.2 g genistein per kg feed) to 61% (2.0 g genistein per kg feed) chemopreventive activity against the carcinogen N-methyl-N-nitrosourea when female Sprague-Dawley rats were given the Teklad rodent diet. No chemopreventive effect was observed with the AIN-76A diet. No toxic effects of genistein were observed with doses of genistein up to 2.0 g/kg feed.

It can be concluded that grape seed extract and genistein are chemopreventive in an animal model of breast cancer and that the chemopreventive action depends on the background diet. The proteins in the Teklad diet (mainly from soy) could enhance the bioavailability of genistein or could have a synergistic bioactive effect with genistein.