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 p53(wt)) 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 p53(wt) cells. Furthermore, results indicate that induction of apoptosis in HCT-116 p53(wt) cells after ibuprofen treatment is in part dependent on a signalling pathway including the neutrophin receptor p75(NTR), p53 and Bax.
pharmazentrum frankfurt/ZAFES, Institut für Klinische Pharmakologie, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, Theodor Stern Kai 7, 60590 Frankfurt/Main, Germany.
Astrid
A
Janssen
Susanne
S
Schiffmann
Kerstin
K
Birod
Thorsten J
TJ
Maier
Ivonne
I
Wobst
Gerd
G
Geisslinger
Sabine
S
Grösch
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D045744:Cell Line, Tumor / Q000378:metabolism* / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D007052:Ibuprofen