| First Author | Lambert JD | Year | 2008 |
| Journal | Carcinogenesis | Volume | 29 |
| Issue | 10 | Pages | 2019-24 |
| PubMed ID | 18684728 | Mgi Jnum | J:140207 |
| Mgi Id | MGI:3812273 | Doi | 10.1093/carcin/bgn182 |
| Citation | Lambert JD, et al. (2008) Effect of genistein on the bioavailability and intestinal cancer chemopreventive activity of (-)-epigallocatechin-3-gallate. Carcinogenesis 29(10):2019-24 |
| abstractText | The green tea (Camellia sinensis) catechin, (-)-epigallocatechin-3-gallate (EGCG), has shown cancer-preventive activity in animal models. Previously, we have reported the bioavailability of EGCG in rats and mice. Here, we report that cotreatment of HT-29 human colon cancer cells with genistein (from soy) increased cytosolic EGCG by 2- to 5-fold compared with treatment with EGCG only. Inclusion of genistein, at non-cytotoxic concentrations, increased the growth inhibitory effects of EGCG against HT-29 cells (up to 2-fold at 20 microM genistein). Intragastric coadministration of EGCG (75 mg/kg) and genistein (200 mg/kg) to CF-1 mice resulted in an increase in plasma half-life (t(1/2) 148.7 +/- 16.4 versus 111.5 +/- 23.4 min) and exposure (AUC(0-->infinity) 183.9 +/- 20.2 versus 125.8 +/- 26.4 microg/ml x min) of EGCG. Cotreatment with genistein also increased the maximal concentration (C(max)), 6 h exposure (AUC(0-->360 min)), and t(1/2) of EGCG in the small intestine by 2.0-, 4.7- and 1.4-fold, respectively, compared with mice treated with EGCG only. Contrary to our expectations, the combination of 0.01% EGCG in the drinking fluid and 0.2% genistein in the diet enhanced intestinal tumorigenesis in male adenomatous polyposis coli (APC)(min/+) mice. This combination increased the multiplicity of tumors in the medial and distal small intestine: the largest increase was in tumors >2 mm in diameter (4.3-fold compared with controls). This study demonstrates that although genistein can enhance EGCG bioavailability and in vitro growth inhibitory activity, this combination enhances tumorigenesis in the APC(min/+) mouse. These results further show the need for careful cancer prevention studies in animal models and for caution when interpreting data from in vitro studies. |
