Cox-2 is needed but not sufficient for apoptosis induced by Cox-2 selective inhibitors in colon cancer cells |
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Authors: | B. Agarwal P. Swaroop P. Protiva S. V. Raj H. Shirin P. R. Holt |
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Affiliation: | (1) Division of Gastroenterology, St. Louis University, School of Medicine, St. Louis, MO, USA;(2) Division of Gastroenterology, Brigham and Women's Hospital, Boston, MA, USA;(3) Division of Gastroenterology, Department of Medicine, St. Luke's-Roosevelt Hospital Center, Columbia University, NY 10025, USA;(4) MD Anderson Cancer Center, Houston, TX, USA |
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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 M decreased cell numbers and induced apoptosis to identical levels in HT29 and HCT116 cells. However, SC236, concentrations >75 M 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 M or sulindac sulfone (SSN) 0–500 M (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 M 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. |
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Keywords: | apoptosis chemoprevention colon cancer curcumin cyclooxygenase |
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