Related Experiment Video
Updated: Aug 9, 2026
Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NFκB Activity and Breast Cancer Stem Cells
Published on: January 18, 2017
Ketoprofen-inhibited N-acetyltransferase activity and gene expression in human colon tumor cells
Kwork-Chu Cheng1, Yu-Ching Li, Chun-Su Yu
1Department of Surgery, Jen-Ai Hospital, 483, Tong-Rong Road, Tali, Taichung, Taiwan, ROC.
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 V(max) 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.
Insights
Ketoprofen inhibits human colon tumor cell arylamine N-acetyltransferase (NAT) activity, gene expression, and DNA adduct formation. This study reveals ketoprofen
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Arylamine N-acetyltransferase (NAT) plays a role in colon tumor development.
- Ketoprofen is known to inhibit aberrant crypt foci in rat colon models.
Purpose of the Study:
- To investigate ketoprofen's effects on human colon tumor cell NAT activity, gene expression, and DNA adduct formation.
- To determine if ketoprofen acts as a competitive inhibitor of NAT enzymes.
Main Methods:
- Utilized human colon adenocarcinoma cell line (colo 205) and cellular cytosols.
- Assessed NAT activity, mRNA NAT expression via PCR, and 2-aminofluorene (AF)-DNA adduct formation.
- Analyzed NAT protein levels using flow cytometry with anti-NAT antibody.
Main Results:
- Ketoprofen inhibited NAT activity in a dose- and time-dependent manner, acting as a competitive inhibitor.
- Ketoprofen decreased AF-DNA adduct formation in colon tumor cells.
- Ketoprofen reduced mRNA NAT expression and the percentage of cells expressing NAT.
Conclusions:
- Ketoprofen demonstrates inhibitory effects on human colon tumor cell NAT activity.
- Ketoprofen impacts NAT gene expression and reduces DNA adduct formation in these cells.
- This is the first study to show ketoprofen's inhibitory action on human colon tumor cell NAT.
Related Concept Videos
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
02:07Tumor Progression
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...