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

Mahnaz Norouzi; Saeed Irian; Adeleh Divsalar; Mona Salimi

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

Author(s):

Mahnaz Norouzi¹,

Saeed Irian¹,

Adeleh Divsalar¹,

Mona Salimi

^2,*

1Department of Biological Sciences, Kharazmi University, Tehran, Iran

2Physiology & Pharmacology Department, Pasteur Institute of, Tehran, Iran

Journal of Reports in Pharmaceutical Sciences:Vol. 2, issue 1; 38-44

Published online:Feb 05, 2013

Article type:Research Article

Received:Jan 09, 2013

Accepted:Jan 29, 2013

How to Cite:Mahnaz NorouziSaeed IrianAdeleh DivsalarMona SalimiA Study on the DNA Cleavage, Morphological Changes and Cytotoxicity Activities of the Two Synthetic COX-2 Inhibitors.J Rep Pharm Sci.2(1):e147760.

Abstract

Celecoxib, a specific cyclooxygenase-2 (COX-2) inhibitor, has been proven 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. The present study is aimed to investigate the morphological changes of cells treated with compounds A and B 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 with 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. Two compounds demonstrated the cytotoxic effects on MCF-7 and K562 cell lines in a concentration-dependent manner with the IC50 values ranging from 6.5 to 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 inhibitor derivatives may present promising chemotherapeutic activities, possibly targeting DNA and inducing cell death in the selected cancer cell line which needs further research.

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