Anti-tumor effect by non-steroidal anti-inflammatory drugs

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We have been reported that etodolac, a chiral non-steroidal anti-inflammatory drug (NSAID) was shown to be pro-apoptotic in primary CLL cells both in vitro and in vivo. Here we also show anti-tumor effect of both the R and S-enatiomers of etodolac against several cancers including neuroblastoma cell line and primary CML cells. Etodolac has additive cytotoxic effects from combinations with other chemotherapeutic drugs such as cyclophosphamide and vincristine. The mechanism of cell death is mitochondrial-dependent pathway because we show that (1) dysfunction of mitochondrial oxygen uptake and membrane potential (2) activation of caspase 9 and caspase 3 (3) degradation of Mcl-1