Journal Article

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

Fan Zhang, Nasser K. Altorki, Juan R. Mestre, Kotha Subbaramaiah and Andrew J. Dannenberg

in Carcinogenesis

Volume 20, issue 3, pages 445-451
Published in print March 1999 | ISSN: 0143-3334
Published online March 1999 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/20.3.445
Curcumin inhibits cyclooxygenase-2 transcription in bile acid- and phorbol ester-treated human gastrointestinal epithelial cells

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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.

Keywords: 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.

Journal Article.  4931 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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