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

• Published in: Cancer letters Vol. 147; no. 1; pp. 95 - 100
• Main Authors: Patten, Emma J, DeLong, Mary J
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 01.12.1999; Elsevier
• Subjects: Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Aspirin - pharmacology; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Carcinogenesis, carcinogens and anticarcinogens; Chemoprevention; Dose-Response Relationship, Drug; Enzyme inducer; Enzyme Induction - drug effects; Foods and miscellaneous; Glutathione S-transferase; Glutathione Transferase - metabolism; HT29 Cells - cytology; HT29 Cells - drug effects; HT29 Cells - enzymology; Humans; Medical sciences; NAD(P)H Dehydrogenase (Quinone) - metabolism; NAD(P)H:quinone reductase; Nonsteroidal anti-inflammatory drug; Pharmacology. Drug treatments; Sulindac - analogs & derivatives; Sulindac - pharmacology; Tumor Cells, Cultured; Tumors; Enzyme inducer; NAD(P)H:quinone reductase; Glutathione S-transferase; Chemoprevention; Nonsteroidal anti-inflammatory drug; Adenocarcinoma; Cell culture; NAD-(P)-H dehydrogenase (quinone); Metabolite; Acetylsalicylic acid; Anticarcinogen; Prevention; Glutathione transferase; Sulindac; Established cell line; Intestinal disease; Indene derivatives; Colon; Salicylates; Tumor cell; Human; Prostaglandin; Enzyme; Transferases; Malignant tumor; Acetic acid derivative; In vitro; Colonic disease; Non steroidal antiinflammatory agent; Digestive diseases; Oxidoreductases
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/S0304-3835(99)00282-7

Non-steriodal anti-inflammatory drugs (NSAIDs) have been found to reduce cancer rates in various segments of the gastrointestinal 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.