Antitumor properties of dimethyl-celecoxib, a derivative of celecoxib that does not inhibit cyclooxygenase-2: implications for glioma therapy

Abstract

Celecoxib (Celebrex) appears to be unique among the class of selective COX-2 inhibitors (coxibs), because this particular compound exerts a second function that is independent of its celebrated ability to inhibit COX-2. This second function is the potential to inhibit cell proliferation and stimulate apoptotic cell death at much lower concentrations than any other coxibs. Intriguingly, these two functions are mediated by different moieties of the celecoxib molecule and can be separated. The author, as well as others, have generated and investigated analogs of celecoxib that retain only one of these two functions. One derivative, 2,5-dimethyl-celecoxib (DMC), which retains the antiproliferative and apoptosis-inducing function, but completely lacks the COX-2 inhibitory activity, is able to mimic faithfully all of the numerous antitumor effects of celecoxib that have been investigated so far, including reduction of neovascularization and inhibition of experimental tumor growth in various in vivo tumor models. In view of the controversy that has recently arisen regarding the life-threatening side effects of this class of coxibs, it may be worthwhile to pursue further the potential benefits of drugs such as DMC for anticancer therapy. Because DMC is not a coxib yet potently maintains celecoxib's antitumor potential, one may be inclined to speculate that this novel compound could potentially be advantageous in the management of COX-2-independent cancers. In this summary, the implications of recent findings with DMC will be presented and discussed.