Abstract
The activation of ketoprofen, which inhibits the outgrowth of azoxymethane-induced aberrant crypt foci in the rat colon, on the inhibition of arylamine N-acetyltransferase (NAT) activity (N-acetylation of substrates), gene expression (mRNA NAT) and 2-aminofluorene (AF)-DNA adduct formation was studied in a human colon tumor (adenocarcinoma) cell line (colo 205). Cellular cytosols (9000 xg supernatant) and intact colon tumor cells were used. The NAT activity in colo 205 cells was inhibited by ketoprofen in a dose- and time -dependent manner in both examined systems. The data also indicated that ketoprofen decreased the apparent value of Vmax of NAT enzymes, being a competitive inhibitor of NAT enzymes. The AF-DNA adduct formation in colo 205 cells was also decreased by ketoprofen. Based on the results from PCR, it was shown that ketoprofen affected mRNA NAT expression in human colon colo 205 cells. The cells were stained with anti-NAT antibody, then analyzed by flow cytometry. The results showed that ketoprofen decreased the percentage of cells stained by anti-NAT. This report is the first to demonstrate that ketoprofen inhibits human colon tumor cell NAT activity, gene expression and DNA adduct formation.
Footnotes
- Received August 22, 2005.
- Revision received December 19, 2005.
- Accepted December 27, 2005.
- Copyright© 2006 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved