Effect of genistein on the bioavailability and intestinal cancer chemopreventive activity of (-)-epigallocatechin-3-gallate

Joshua D. Lambert, Seok Joo Kwon, Jihyeung Ju, Mousumi Bose, Mao Jung Lee, Jungil Hong, Xingpei Hao, Chung S. Yang

Research output: Contribution to journalArticle

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Abstract

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 μM 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 (t1/2 148.7 ± 16.4 versus 111.5 ± 23.4 min) and exposure (AUC0→∞ 183.9 ± 20.2 versus 125.8 ± 26.4 μg/ml × min) of EGCG. Cotreatment with genistein also increased the maximal concentration (Cmax), 6 h exposure (AUC0→360min), and t1/2 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 APCmin/+ 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.

Original languageEnglish (US)
Pages (from-to)2019-2024
Number of pages6
JournalCarcinogenesis
Volume29
Issue number10
DOIs
StatePublished - Oct 13 2008

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Intestinal Neoplasms
Genistein
Biological Availability
Small Intestine
Neoplasms
Carcinogenesis
epigallocatechin gallate
Animal Models
Camellia sinensis
HT29 Cells
Adenomatous Polyposis Coli
Catechin
Tea
Growth
Colonic Neoplasms
Drinking
Half-Life

All Science Journal Classification (ASJC) codes

  • Cancer Research

Cite this

Lambert, Joshua D. ; Kwon, Seok Joo ; Ju, Jihyeung ; Bose, Mousumi ; Lee, Mao Jung ; Hong, Jungil ; Hao, Xingpei ; Yang, Chung S. / Effect of genistein on the bioavailability and intestinal cancer chemopreventive activity of (-)-epigallocatechin-3-gallate. In: Carcinogenesis. 2008 ; Vol. 29, No. 10. pp. 2019-2024.
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abstract = "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 μM 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 (t1/2 148.7 ± 16.4 versus 111.5 ± 23.4 min) and exposure (AUC0→∞ 183.9 ± 20.2 versus 125.8 ± 26.4 μg/ml × min) of EGCG. Cotreatment with genistein also increased the maximal concentration (Cmax), 6 h exposure (AUC0→360min), and t1/2 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 APCmin/+ 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.",
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Effect of genistein on the bioavailability and intestinal cancer chemopreventive activity of (-)-epigallocatechin-3-gallate. / Lambert, Joshua D.; Kwon, Seok Joo; Ju, Jihyeung; Bose, Mousumi; Lee, Mao Jung; Hong, Jungil; Hao, Xingpei; Yang, Chung S.

In: Carcinogenesis, Vol. 29, No. 10, 13.10.2008, p. 2019-2024.

Research output: Contribution to journalArticle

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T1 - Effect of genistein on the bioavailability and intestinal cancer chemopreventive activity of (-)-epigallocatechin-3-gallate

AU - Lambert, Joshua D.

AU - Kwon, Seok Joo

AU - Ju, Jihyeung

AU - Bose, Mousumi

AU - Lee, Mao Jung

AU - Hong, Jungil

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AU - Yang, Chung S.

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