In vivo and in vitro effects of ellagic acidon N-acetyltransferase activity

• Main Authors: Ho, Chin-Chin, 何蓁蓁
• Other Authors: Tsai, Huei-Yann
• Format: Others
• Language: zh-TW
• Published: 2000
• Online Access: http://ndltd.ncl.edu.tw/handle/59321905148819274167

博士 === 中國醫藥學院 === 中國藥學研究所 === 88 === The determinations of N-acetyltransferase (NAT) activities in cytosol and intact cells were analyzed by using acetyl-CoA recycling mixture assay and high performance liquid chromatography (HPLC). The effects of ellagic acid (EA) on arylamine N-acetyltransferase (NAT) activities and kinetic constant changes of NAT enzyme from blood, liver, bladder, colon, urine, feces, and leukocytes (i.e. lymphocytes and monocytes) of Sprague-Dawley (SD) rats and also in human colon tumor cell line (colo 205) were determined. The results indicated that there were a decreasing of NAT activities and kinetic constant changes of NAT associated with increased level of EA in the cytosol or intact cells of examined tissues or cells. EA was an uncompetitive inhibitor for examined NAT enzyme. The cell cycle of human colon tumor cell (colo 205) treated with various concentrations of EA for different time was determined. The cell cycle analysis was based on the cell numbers of DNA content by using flow cytometry analysis. The results also showed that the treatment of 5,50,100,250 and 500 µM EA for 12,24,48 and 72 hours in human colon tumor cells resulted in the inhibition of S phase which may be via the arresting cell cycle at G0/G1 (p<0.05). The effects of EA orally on 2-aminofluorene (2-AF) N-acetylation and metabolism in SD rats were examined. It was indicated that 24 hours after EA treatment then oral treatment of 2-AF for 24 hours, The 2-AAF and 2-AF metabolites from bladder tissues showed a significant difference between control and experimental groups. But the treatment of EA and 2-AF at the same time to the rats, the decrease in 2-AF metabolites from urine and feces showed a significant difference between control and experimental groups. The inhibitory level of NAT by EA from experimental groups was treatment of EA and 2-AF treatment at the same time > 24 hours after EA treatment then treated with 2-AF > 2-AF treatment alone (control). In conclusion, these results indicated that EA could decrease NAT activity and inhibit S phase of cell cycle of human colon tumor cells.