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Celecoxib has been demonstrated as a good chemopreventive agent in retrospective studies and clinical trials. Recent research suggests that structural modification of this molecule may enhance this effect at lower physiological doses. The present study focuses on the growth inhibiting and apoptotic mechanisms of celecoxib derivative OSU03012 in human oral cell lines. Premalignant, malignant and normal human oral epithelial cell lines were treated with 0-10 μM OSU03012 for 3 days. Growth inhibition assays showed that it selectively inhibited the growth of premalignant and malignant cell lines. Flow cytometry analyses revealed that OSU03012 induced an S phase block in both premalignant and malignant cell, but not in normal cells. Western blot analyses indicated that OSU03012 increases the protein levels of cyclin A, cyclin B, cdk2 and cdc2 and reduced the levels of p21WAF1. These changes in cell cycle progression and regulatory proteins corresponded to the induction of apoptosis characterized by morphological change, increased activity of caspase 3, and cleavage of PAPR. These results suggest that this novel celecoxib derivative selectively inhibit premalignant and malignant human oral cell growth by inducing cell cycle arrest and apoptosis. Supported by NCI CA109012 and CA94829, and NIDCR P01-DE12704.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]