imatinib and its combination with 2,5-dimethyl-celecoxib induces apoptosis of human ht-29 colorectal cancer cells

نویسندگان

somayeh atari-hajipirloo 1department of biochemistry , student research committee,urmia university of medical sciences, urmia, i.r. iran.

saba nikanfar 2department of biochemistry, urmia university of medical sciences, urmia, i.r. iran.

amir heydari 3department of pharmacology, cellular and molecular research center, urmia university of medical sciences, urmia, i.r. iran.

fatemeh kheradmand 4department of clinicalbiochemistry, cellular and molecular and solid tumor research center, urmia university of medical sciences, urmia, i.r. iran.

چکیده

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 ic 50 dose of imatinib (6.60 µm), dmc (23.45 µm), and their combination (half dose of ic 50 ) 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.

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عنوان ژورنال:
research in pharmaceutical sciences

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