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Green tea has been shown to have many beneficial health effects. We have previously reported that dietary (-)-epigallocatechin-3-O-gallate (EGCG), the major polyphenol in green tea, reduced gene expressions of gluconeogenic enzymes, glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK), in the normal mouse liver. In the present study, we examined the effects of intragastrical administration of EGCG on the expression of gluconeogenesis-related genes in the mouse intestine. The results of experiments with the semi-quantitative reverse transcription-polymerase chain reaction indicated that EGCG at 0.6 mg/head caused a reduced expression of G6Pase, PEPCK, hepatocyte nuclear factor 1α (HNF1α), and HNF4α. Experiments using the quantitative real-time polymerase chain reaction confirmed these effects. We then examined the effects of EGCG using human colon carcinoma Caco-2 cells stimulated with dexamethasone and dibutyryl cAMP. The results were generally consistent with those from the experiments in vivo. The present findings suggest EGCG to contribute to the beneficial effects of green tea on diabetes, obesity, and cancer by modulating gene expression in the intestine.

Rat hepatoma H4IIE cells were stimulated with dexamethasone and dibutyryl cAMP to increase gene expressions of gluconeogenic enzymes, glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK). Inclusion of catechin-rich green tea beverage (GTB) in the culture medium reduced the up-regulation of these genes as well as that of hepatocyte nuclear factor 4 alpha (HNF4alpha) gene. GTB was fractionated into chloroform-soluble (Fraction I), ethyl acetatesoluble (Fraction II), methanol-soluble (Fraction III) and residual (Fraction IV) fractions. Fractions II and III containing catechins caused an attenuation of the up-regulated expression of these genes as well as the down-regulation of HNF4alpha gene expression. Fraction IV had a synergistic effect on the up-regulation by dexamethasone/dibutyryl cAMP of the PEPCK gene expression and upregulated HNF4alpha gene expression. These results suggest that GTB down-regulated the expression of the HNF4alpha gene to cause the down-regulated gene expression of gluconeogenic enzymes. One reason why GTB did not down-regulate hepatic PEPCK gene expression in previous animal experiments may be that the component(s) acting to up-regulate PEPCK gene expression was more effective in vivo than in cultured cells.

Employing the DNA microarray technique, we previously reported the alteration in gene expression of nucleocytoplasmic transport factors, importins and exportins, induced by 1,25-dihydroxyvitamin D3 (DVD) in human leukemia HL-60 cells. Here, we used the quantitative reverse transcription-polymerase chain reaction method to confirm such previous findings, and compared them with those from the cells treated with all-trans-retinoic acid (ATRA). The results indicated that the gene expression of the transport factors examined was mostly down-regulated following differentiation induced by DVD and ATRA, but importin alpha5 gene expression was up-regulated in either case. The differences were found in the gene expression of importin alpha3 and exportin 6 between the cells after treatments with DVD and ATRA. These variations may be related to the difference between HL-60 cell lineages differentiating into monocytes/macrophages and granulocytes. The present findings provide further evidence to support the important roles of importins and exportins in cell differentiation.