Antitumor effect of a newly synthesized celecoxib derivative encapsulated in liposome

Abstract

A new cyclooxygenase-2 inhibitor (code: PCX-3) was synthesized as a sodium salt form of celecoxib, a non-steroidal anti-inflammatory drug (NSAID), and tested for its anticancer activity using human colon adenocarcinoma cells (HT-29) in vitro. Anti-proliferative effect of HT-29 cells by PCX-3 in DPPC/Chol liposomes was more effective than the free PCX-3 by 2-folds (IC30 = 125 μM vs. 227.5 μM). The same liposomal formulation of PCX-3 also showed a 2-fold increased effect than the free one both in DNA fragmentation and caspase activity of HT-29 cells at 19-743 μM and 37-371 μM ranges, respectively, suggesting apoptosis-based anti-proliferative effect. Down regulation of prostaglandin E2 level of HT-29 cells by the treatment of liposomal PCX-3 was more profound than its free form at 0.001-0.002 μM range. These data suggest that the liposomal formulation of this newly synthesized PCX-3 could be re-visited as a new anticancer or chemo-preventive agent in the future. © 2013 The Korean Society of Pharmaceutical Sciences and Technology.