title: Imatinib and its combination with 2,5-dimethyl-celecoxibinduces apoptosis of human HT-29 colorectal cancer cells.
abstract: Mono-targeting by imatinib as a main antitumor agent does not always accomplish complete cancer suppression. 2,5-dimethyl-celecoxib (DMC) is a close structural analog of the selective cyclooxygenase-2 (COX-2) inhibitor, celecoxib, that lacks COX-2 inhibitory function. In this study, we aimed to show the apoptotic effects of imatinib in combination with DMC in human HT-29 colorectal cancer (CRC) cells. HT-29 CRC cells were treated with IC50dose of imatinib (6.60 μM), DMC (23.45 μM), and their combination (half dose of IC50) for 24 h. The caspase-3 activity was estimated with colorimetric kit. The caspase-3 gene expression was evaluated by real-time PCR method. There was a significant up-regulation in caspase-3 enzyme activity and caspase-3 expression by imatinib and its half dose combination with DMC as compared to control. As a summary, the results of this study strongly suggest that half dose combination of imatinib with DMC induced apoptosis as potent as full dose imatinib in human HT-29 CRC cells, while minimizing undesired side effects related to imatinib mono-therapy. This study also pointed towards possible caspase-dependent actions of imatinib and DMC.
authors.affiliation: Department of Biochemistry, Student Research Committee, Urmia University of Medical Sciences, Urmia, I.R. Iran.
authors.forename: Somayeh
authors.initials: S
authors.lastname: Atari-Hajipirloo
authors.affiliation: Department of Biochemistry, Urmia University of Medical Sciences, Urmia, I.R. Iran.
authors.forename: Saba
authors.initials: S
authors.lastname: Nikanfar
authors.affiliation: Department of Pharmacology, Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, I.R. Iran.
authors.forename: Amir
authors.initials: A
authors.lastname: Heydari
authors.affiliation: Department of Clinical Biochemistry, Cellular and Molecular and Solid Tumor Research Center, Urmia University of Medical Sciences, Urmia, I.R. Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Kheradmand
keywords: Apoptosis; Colorectal cancer cell line.; Dimethyl-celecoxib; Gene expression; Imatinib