p53 is important for the anti-proliferative effect of ibuprofen in colon carcinoma cells

S-ibuprofen which inhibits the cyclooxygenase-1/-2 and R-ibuprofen which shows no COX-inhibition at therapeutic concentrations have anti-carcinogenic effects in human colon cancer cells; however, the molecular mechanisms for these effects are still unknown. Using HCT-116 colon carcinoma cell lines, expressing either the wild-type form of p53 (HCT-116 p53wt) or being p(HCT-116 p53−/−), we demonstrated that both induction of a cell cycle block and apoptosis after S- and R-ibuprofen treatment is in part dependent on p53. Also in the in vivo nude mice model HCT-116 p53−/− xenografts were less sensitive for S- and R-ibuprofen treatment than HCT-116 p53wt cells. Furthermore, results indicate that induction of apoptosis in HCT-116 p53wt cells after ibuprofen treatment is in part dependent on a signalling pathway including the neutrophin receptor p75NTR, p53 and Bax.