Cox-2 is needed but not sufficient for apoptosis induced by Cox-2 selective inhibitors in colon cancer cells

Apoptosis. 2003 Dec;8(6):649-54. doi: 10.1023/A:1026199929747.


The role of Cox-2 in NSAID-induced apoptosis is debated. We studied the role of Cox-2 inhibition in apoptosis induced by a selective Cox-2 inhibitor, SC236 (a structural analogue of celecoxib) in two colon cancer cell lines, HT29 (expressing Cox-2 protein) and HCT116 (not expressing Cox-2 protein). Apoptosis was quantified by flow cytometry. SC236 0-75 microM decreased cell numbers and induced apoptosis to identical levels in HT29 and HCT116 cells. However, SC236, concentrations >75 microM reduced Cox-2 protein expression in HT29 cells and induced greater levels of apoptosis in HT29 than in HCT116 cells. In contrast, sulindac sulfide (SSD) (which inhibits Cox-1 and Cox-2) 0-200 microM or sulindac sulfone (SSN) 0-500 microM (without significant activity against Cox-1 or Cox-2) caused identical decreases in cell number and increases in apoptosis in HT29 and HCT116 cells. Neither SSD nor SSN altered the expression of Cox-2 in HT29 cells. To determine that the higher levels of apoptosis in HT29 cells with SC236 >75 microM were related to decreased Cox-2 protein levels, we decreased Cox-2 protein expression in HT29 cells with curcumin (diferuloylmethane) and studied its effect on SC236-induced apoptosis. Curcumin augmented apoptosis induced by SC236 in HT29 cells but not in Cox-2 lacking HCT116 cells. In conclusion, selective Cox-2 inhibitors can induce apoptosis independent of Cox-2 expression. However they may selectively target cells that express Cox-2 by decreasing their Cox-2 protein expression.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Colonic Neoplasms / drug therapy*
  • Curcumin / pharmacology
  • Cyclooxygenase 2
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / metabolism*
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Pyrazoles / pharmacology
  • Sulfonamides / pharmacology
  • Sulindac / analogs & derivatives*
  • Sulindac / pharmacology


  • 4-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide
  • Antineoplastic Agents
  • Isoenzymes
  • Pyrazoles
  • Sulfonamides
  • Sulindac
  • sulindac sulfide
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Curcumin
  • sulindac sulfone