Cytotoxicity of Clinically-Used Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in the Human Bladder Cancer Cell Line UM-UC-3

Abstract

We evaluated 8 clinically-used non-steroidal anti-inflammatory drugs (NSAIDs): Aspirin, Etodolac, Diclofenac, Ibuprofen, Indomethacin, Mefenamic acid, Nabumetone, and Piroxicam, for cytotoxicity in the human bladder cancer cell line UM-UC-3 in vitro. Basing our dosages on the maximum concentration of each NSAID used clinically, four concentrations of each drug were prepared, and the viability of UM-UC-3 cells given each treatment was monitored for up to 5 days. At the highest concentration, Aspirin and Diclofenac caused no decrease in UM-UC-3 viability during the 5-day incubation. Etodolac, Ibuprofen, Indomethacin, and Piroxicam decreased the viability of UM-UC-3 cells about 20% on the fifth day. Treatment with 30 µg/ml of Mefenamic acid and 16 µg/ml of Nabumetone caused about a 40% loss of cell viability on the last day of the experiment. Thus, the most effective cytotoxicity was observed with Mefenamic acid and Nabumetone. We then examined the nature of the cell death induced by these two drugs, by biochemical and morphological analyses. A DNA fragmentation assay showed DNA-ladder formation with both Mefenamic acid and Nabumetone treatment. In addition, nuclear blebbing was observed by fluorescence microscopy in both Mefenamic acid- and Nabumetone-treated cells. Since DNA ladder formation and nuclear blebbing are hallmarks of typical apoptotic cell death, we concluded that at least two NSAIDs, Mefenamic acid and Nabumetone, could cause apoptotic cell death in the human bladder cell line, UM-UC-3.