Effects of sulindac, sulindac metabolites, and aspirin on the activity of detoxification enzymes in HT-29 human colon adenocarcinoma cells

Non-steriodal anti-inflammatory drugs (NSAIDs) have been found to reduce ca ncer rates in various segments of the gastrointestinal tract in both animal s and humans. In this study we examined the effect of sulindac, sulindac su lfide, sulindac sulfone and aspirin on QR and GST activity. We found that s ulindac itself increased QR activity as much as 2-fold over controls but ha d no effect on GST activity. Sulindac sulfone, a metabolite of sulindac whi ch 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 G ST to 1.5-fold and 3.5-fold over controls respectively. These data indicate that NSAIDs increase phase II enzyme detoxification enzyme activity. Conse quently, this effect may contribute to the protective effect of NSAIDs agai nst colon cancer and may be an anticarcinogenic effect of these drugs that is distinct from their ability to inhibit PG synthesis. (C) 1999 Elsevier S cience Ireland Ltd. All rights reserved.