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Apoptosis

, Volume 8, Issue 6, pp 649–654 | Cite as

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

  • B. AgarwalEmail author
  • P. Swaroop
  • P. Protiva
  • S. V. Raj
  • H. Shirin
  • P. R. Holt
Article

Abstract

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 μM decreased cell numbers and induced apoptosis to identical levels in HT29 and HCT116 cells. However, SC236, concentrations >75 μM 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 μM or sulindac sulfone (SSN) 0–500 μM (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 μM 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.

apoptosis chemoprevention colon cancer curcumin cyclooxygenase 

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Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  • B. Agarwal
    • 1
    Email author
  • P. Swaroop
    • 2
  • P. Protiva
    • 3
  • S. V. Raj
    • 4
  • H. Shirin
    • 3
  • P. R. Holt
    • 3
  1. 1.Division of GastroenterologySt. Louis University, School of MedicineSt. LouisUSA
  2. 2.Division of GastroenterologyBrigham and Women's HospitalBostonUSA
  3. 3.Division of Gastroenterology, Department of Medicine, St. Luke's-Roosevelt Hospital CenterColumbia UniversityUSA
  4. 4.MD Anderson Cancer CenterHoustonUSA

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