Superior effectiveness of ibuprofen compared with other NSAIDs for reducing the survival of human prostate cancer cells.
OBJECTIVE
Although NSAIDs (nonsteroidal antiinflammatory drugs) appear to be effective in the prevention and treatment of prostate cancer, very little information exists on the comparative effects of common nonprescription NSAIDs. In the present investigation, we evaluated the effects of widely used nonprescription NSAIDs on human prostate cancer cells in vitro.


METHODS
Using in vitro models of androgen-sensitive and androgen-insensitive human prostate cancer cells, we evaluated the effects of acetaminophen, aspirin, naproxen, and ibuprofen on cell survival, cell cycle and the induction of apoptosis. We also compared the effects of these drugs with that of the selective cyclooxygenase-2 (COX-2) inhibitor, NS-398.


RESULTS
Ibuprofen was significantly more effective against human prostate cancer cells in vitro than the other tested nonprescription NSAIDs. MTT analysis indicated that clinically relevant concentrations of ibuprofen significantly reduced the survival of LNCaP human prostate tumor cells. TUNEL analysis demonstrated that this was due in part to a significant number of LNCaP cells undergoing apoptosis. Ibuprofen also induced the same amount of apoptosis of an androgen-independent human prostate cancer cell line (DU-145), but had little effect on normal mouse fibroblast (3T3) cells. Cell cycle analysis indicated that ibuprofen caused LNCaP cells to shift from the S and G(2)/M phases to the G(0)/G(1) phases of the cell cycle. Another propionic acid NSAID, naproxen, had an effect similar to but overall less than that of ibuprofen. Suprapharmacological concentrations of aspirin and acetaminophen did not induce levels of apoptosis in LNCaP cells similar to those induced by clinically relevant concentrations of ibuprofen. The selective COX-2 inhibitor NS-398 mirrored the effectiveness of ibuprofen against LNCaP cells in vitro. However, when the pharmacokinetics of selective COX-2 inhibitors and other NSAIDs reported to be effective against prostate cancer were taken into consideration, ibuprofen appeared to be one of the most effective NSAIDs at clinically relevant concentrations.


CONCLUSIONS
These observations support the use of ibuprofen in future in vivo studies and in clinical trials designed to test the effectiveness of NSAIDs against human prostate cancer.
D000082:Acetaminophen; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D009288:Naproxen / Q000494:pharmacology; D009578:Nitrobenzenes / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013449:Sulfonamides / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D000082:Acetaminophen; D009288:Naproxen; D001241:Aspirin; D007052:Ibuprofen