A Study on the DNA Cleavage, Morphological Changes and Cytotoxicity Activities of the Two Synthetic COX-2 Inhibitors

Celecoxib, a specific cyclooxygenase-2 (COX-2) inhibitor, has been shown to possess antitumor activity in a variety of cancer cells. However, the antitumor activity of two synthesized COX-2 inhibitor derivatives (A and B) on human myeloid leukemia (K562) and breast adenocarcinoma (MCF-7) cancer cells has not been well established. This study was designed to investigate the morphological changes of compounds A and B –treated cells as well as DNA cleavage activity of these compounds. The DNA cleavage experiments were performed by agarose gel electrophoresis. Plasmid pTZ57 DNA was treated with the compounds A and B at various concentrations. Then, bands visualized by UV light and photographed to determine the extent of cleavage of the supercoiled (SC) to Nicked (NC) DNA. Furthermore, the apoptotic activities of the two compounds were assessed using cells treated DAPI staining method. The results obtained from DNA cleavage assay demonstrated that with the increasing concentration of compound A, SC DNA is gradually converted to NC DNA. Cells were also exposed to various concentrations (0.1-100 μM) of each compound for 24 h. All compounds demonstrated remarkable cytotoxic effect on MCF-7 and K562 cell lines in a concentration-dependent manner with IC50 values ranging between 6.5–22.23 μM. Treatment of the cells with compounds A and B significantly cause morphological changes after 16 h. Collectively, our data indicate that compounds A and B as two COX-2 derivatives may present promising chemotherapeutic agents, possibly targeting DNA and inducing cell death in the selected cancer cell line which needs further research.