Carcinogenesis, Vol. 20, No. 3, 445-451,
March 1999
© 1999 Oxford University Press
Curcumin inhibits cyclooxygenase-2 transcription in bile acid- and phorbol ester-treated human gastrointestinal epithelial cells
1 Department of Cardiothoracic Surgery and
2 Departments of Medicine and Surgery, New York Presbyterian Hospital and Weill Medical College of Cornell University, New York, NY 10021,
3 Head and Neck Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 and
4 Anne Fisher Nutrition Center at Strang Cancer Prevention Center, New York, NY 10021, USA
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.
Abbreviations: AP-1, activator protein-1; CD, chenodeoxycholate; COX, cyclooxygenase; DMEM, Dulbecco's modified Eagle's medium; FCS, fetal calf serum; LDH, lactate dehydrogenase; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylltetrazolium bromide; NSAIDs, non-steroidal anti-inflammatory drugs; PG, prostaglandin; PKC, protein kinase C; PMA, phorbol 12-myristate 13-acetate.
5 To whom correspondence should be addressed at: New York Presbyterian Hospital–Cornell Campus, Division of Gastroenterology and Hepatology, Room F-231, 1300 York Avenue, New York, NY 10021, USA Email: ajdannen{at}mail.med.cornell.edu
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