Soy isoflavones genistein prevents while daidzein promotes metastatic breast cancer progression

1255

Soy foods have gained popularity with the public due to reports of decreased breast cancer incidence among Asian women who consume more soy than Western women. Even though a large body of data has been generated on the role of soy compounds in cancer prevention, the current literature does not allow for definitiveconclusions on the effect of soy foods in high-risk women or survivors of breast cancer. Moreover, most studies on the effects of dietary soy consumption on breast cancer have focused on prevention of breast cancer initiation and not their effects on metastasis, the most deadly aspect of the disease. Studies with the more abundant soy isoflalvone genistein (50% of total soy isoflavones) have shown that genistein reduces breast cancer metastasis in mouse models; however, the effect of the next abundant soy isoflavone daidzein (40% of total soy isoflavones) has not been testedspecifically for breast cancer metastasis. To investigate a role for genistein and dadizein in metastatic breast cancer, we tested the effect of dietary administration of genistein or daidzein in the nude mouse model of experimental metastasis. Tumors were established in the mammary fat pad of female athymic nude mice using a GFP-tagged highly metastatic variant of the MDA-MB-435 cell line. Mice were administered vehicle or 5 mg/kg genistein or daidzein 3X a week for 2.5 months. Primary mammary tumor and metastatic progression was imaged using an in situ whole body fluorescence imaging system and quantified by the pixel intensity of digital images. At the end of the study, distant organs were isolated and analyzed for metastases using fluorescence image analysis. Our results show that genistein decreased primary mammary growth while daidzein increased primary mammary growth in a statistically significant manner. Similarly, genistein decreased metastasis to distant sites while daidzein increased the number of metastases compared to control. Therefore, this study demonstrates that genistein can be used as an effective breast cancer metastasis preventive. However, consumption of soy foods that also contain daidzein may not be a safe alternative for breast cancer patients, survivors, and those at high risk for breast cancer. This study was funded by AICR IIG 03-31-06 to S.D.and NIH/RCMI 2G12RR003035 to UCC.