Curcumin inhibits cyclooxygenase-2 transcription in bile acid- and phorbol ester-treated human gastrointestinal epithelial cells

• Published in: Carcinogenesis (New York) 1999-03, Vol.20 (3), p.445-451
• Main Authors: Zhang, Fan, Altorki, Nasser K., Mestre, Juan R., Subbaramaiah, Kotha, Dannenberg, Andrew J.
• Format: Article
• Language: English
• Subjects: 5-dimethylthiazol-2-yl)-2; 5-diphenylltetrazolium bromide; activator protein-1; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anticarcinogenic Agents - pharmacology; AP-1; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Chemical agents; chenodeoxycholate; Chenodeoxycholic Acid - pharmacology; COX; Curcumin - pharmacology; cyclooxygenase; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - pharmacology; Digestive System - cytology; Digestive System - drug effects; Digestive System - enzymology; DMEM; Dulbecco's modified Eagle's medium; Enzyme Induction; FCS; fetal calf serum; Gastric Mucosa - drug effects; Gastric Mucosa - enzymology; Humans; Intestinal Mucosa - drug effects; Intestinal Mucosa - enzymology; Isoenzymes - biosynthesis; Isoenzymes - genetics; lactate dehydrogenase; LDH; Medical sciences; Membrane Proteins; MTT; non-steroidal anti-inflammatory drugs; NSAIDs; phorbol 12-myristate 13-acetate; PKC; PMA; prostaglandin; Prostaglandin-Endoperoxide Synthases - biosynthesis; Prostaglandin-Endoperoxide Synthases - genetics; protein kinase C; RNA, Messenger - genetics; Tetradecanoylphorbol Acetate - pharmacology; Transcription, Genetic - drug effects; Tumors
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/20.3.445

We investigated whether curcumin, a chemopreventive agent, inhibited chenodeoxycholate (CD)- or phorbol ester (PMA)-mediated induction of cyclooxygenase-2 (COX-2) in several gastrointestinal cell lines (SK-GT-4, SCC450, IEC-18 and HCA-7). Treatment with curcumin suppressed CD- and PMA-mediated induction of COX-2 protein and synthesis of prostaglandin E2. Curcumin also suppressed the induction of COX-2 mRNA by CD and PMA. Nuclear run-offs revealed increased rates of COX-2 transcription after treatment with CD or PMA and these effects were inhibited by curcumin. Treatment with CD or PMA increased binding of AP-1 to DNA. This effect was also blocked by curcumin. In addition to the above effects on gene expression, we found that curcumin directly inhibited the activity of COX-2. These data provide new insights into the anticancer properties of curcumin.