Effects of sulindac, sulindac metabolites, and aspirin on the activity of detoxification enzymes in HT-29 human colon adenocarcinoma cells.
Non-steroidal anti-inflammatory drugs (NSAIDs) have been found to reduce cancer rates in various segments of the gastro-intestinal tract in both animals and humans. In this study we examined the effect of sulindac, sulindac sulfide, sulindac sulfone and aspirin on QR and GST activity. We found that sulindac itself increased QR activity as much as 2-fold over controls but had no effect on GST activity. Sulindac sulfone, a metabolite of sulindac which lacks the ability to inhibit prostaglandin (PG) synthesis, increased QR and GST to 1.5-fold over controls in both cases. Aspirin increased QR and GST to 1.5-fold and 3.5-fold over controls respectively. These data indicate that NSAIDs increase phase II enzyme detoxification enzyme activity. Consequently, this effect may contribute to the protective effect of NSAIDs against colon cancer and may be an anticarcinogenic effect of these drugs that is distinct from their ability to inhibit PG synthesis.
Patten
E J
EJ
Department of Environmental and Occupational Health, School of Public Health, Emory University, Atlanta, GA 30322, USA. epatten@emory.edu
DeLong
M J
MJ
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D005982:Glutathione Transferase / Q000378:metabolism; D019073:HT29 Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D006801:Humans; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D013467:Sulindac / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013467:Sulindac; C025462:sulindac sulfide; D016660:NAD(P)H Dehydrogenase (Quinone); D005982:Glutathione Transferase; C025463:sulindac sulfone; D001241:Aspirin