Dimethyl-celecoxib (DMC), a derivative of celecoxib that lacks cyclooxygenase-2-inhibitory function, potently mimics the anti-tumor effects of celecoxib on Burkitt's lymphoma in vitro and in vivo.

The nonsteroidal anti-inflammatory drug (NSAID) celecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor that has shown some promising results as an anti-cancer drug. However, the question arose as to whether or not its COX-2-inhibitory function is required for its anti-tumorigenic properties. We therefore employed dimethyl-celecoxib (DMC), which is a close structural analog of celecoxib that lacks COX-2-inhibitory function, to investigate this question. By performing a combination of in vitro and in vivo studies with Burkitt's lymphoma cells, we found that DMC potently mimics all of the anti-proliferative and anti-tumorigenic effects of celecoxib. In cell culture, DMC effectively inhibits cell proliferation through the down-regulation of cyclins A and B and the ensuing loss of cyclin-dependent kinase activity. This effect appears to take place in vivo as well and results in significantly (p<.002) reduced tumor growth in experimental animals. Thus, our results demonstrate that the anti-proliferative and anti-tumorigenic properties of celecoxib and DMC are indistinguishable, at least in Burkitt's lymphoma cells, and therefore, that the COX-2-inhibitory function is not required for these effects.