Cyclooxygenase-2 inhibition by novel Bisaryl imidazolyl imidazole derivatives increases Bax/Bcl-2 ratio and upregulates Caspase-3 gene expression in Caco-2 colorectal cancer cell line

Abstract

Cyclooxygenase-2 (COX-2) inhibitors including celecoxib inhibit cell growth and induce apoptosis in cancer cells. In this study, the relation of Bax (an apoptosis promoter) to Bcl-2 (an apoptosis inhibitor) ratio with the apoptosis co-ordination enzyme, caspase-3 was investigated in correlation with the treatment of 4,5-bisaryl imidazolyl imidazoles as novel selective COX-2 inhibitors in Caco-2 colorectal cancer cells. Recently, the organic reactions under microwave irradiation attracted attention of scientists due to their high reaction rate, mild reaction conditions and the formation of clean products. Therefore, a microwave-assisted method was used to synthesize our compounds. The effects of these COX-2 inhibitors on the proliferation of Caco-2 cells were evaluated by MTT assay. cDNA microarray and clustering analysis were used to evaluate effects of our synthetic compounds on gene expression pattern of 112 genes involved in apoptosis pathways. Bax, Bcl-2 and caspase-3 mRNA expression and their relationship were analyzed by quantitative real-time PCR. Results indicated that proliferation of Caco-2 cells after treatment with 4,5-bisaryl imidazolyl imidazoles on Caco-2 cells were time and dose dependent. We conclude that increase in Bax/Bcl-2 ratio leads to an up-regulation in caspase-3 mRNA expression.