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, Andrew J. Dannenberg
1999 Carcinogenesis  
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 E 2 . Curcumin also suppressed the induction of COX-2 mRNA by CD and PMA. Nuclear run-offs revealed increased rates of COX-2 transcription after
more » ... scription 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.
doi:10.1093/carcin/20.3.445 pmid:10190560 fatcat:kqxst2k4lvhr5kgwjrpixhonna