Title details Help Title Mechanisms of hypoxia selectivity and DNA damage by 2-benzoyl-6,7-dichloro-3-phenylquinoxaline 1,4-dioxide in human colon cancer cells / by Mona Mohamad El Khatib Thesis Name(s) El Khatib, Mona Mohamad (Main Author) American University of Beirut. Faculty of Arts and Sciences. Department of Biology (Related name) Publication 2009 Link(s) Click for full-text Physical Details xvii, 80 leaves; ill. (some col.); 30 cm. Subjects Colon (Anatomy)--Cancer Tumors Cancer cells DNA damage Quinoxaline Classmarks T:005296 Notes Dissertation: Thesis (M.S.)--American University of Beirut, Dept. of Biology, 2009. Dissertation: Advisor : Dr. Hala Gali-Muhtasib, Professor , Biology Member of Committee : Dr. Rabih Talhouk, Professor , Biology Member of Committee : Dr. Fady Geara, Professor , Radiology. Bib. & Index: Bibliography : leaves 75-80. Abstract DCQ (2-benzoyl-6,7-dichloro-3-phenylquinoxaline 1,4-dioxide) is a synthetic quinoxaline that enhances the sensitivity of cancerous cells to hypoxia. The aim of this study is to clarify the DNA damage potential and mechanism of anticancer action of DCQ under oxic and hypoxic conditions in HCT116 human colorectal cancer cell lines that differ in their p53 and p21 status. We observed that the hypoxic cytotoxicity and DNA damaging potential of DCQ in HCT116 cells is dependent on the drug concentration and the oxygenation status of the cells. DCQ decreased the proliferation and colony forming ability of the three HCT116 (p53+/+, p53-/- and p21-/-) cells under both oxia and hypoxia. The cytotoxicity of DCQ was slightly greater under hypoxia than oxia; the HCR values ranges from 1.17 to 1.5. Interestingly, DCQ has no cytotoxic effect on FHs74 Int normal human intestinal cell line. We show that one of the mechanisms through which DCQ exerts its hypoxic selectivity is through the decrease in HIF-1 alpha protein expression. We also show that DCQ enhances the formation of SSB more so under hypoxia than oxia. In addition, DCQ was found to increase the expression of the proapoptotic caspase-2 and to inhibit the activation of the prosurvival protein PIDD-C in HCT116 p53+/+ cells, therefore, causing apoptosis. DCQ induced different modes of cell death depending on the drug concentration used. Higher doses of DCQ induced apoptosis while lower doses caused mitotic catastrophe. While exposure of DCQ-treated cells to hypoxia resulted in apoptosis in HCT-116 p53+/+ cells, G2/M arrest was the prevailing response in DCQ-treated cells exposed to oxic conditions. In conclusion, the ability of DCQ to induce DNA damage and to reduce HIF-1 alpha protein expression in more than one colon cancer cell line makes it an interesting molecule with potential anticancer activities against colon cancer Availability Barcode Location Shelf Shelfmark Status Category   Jafet Archives and Special Collections Thesis T:5296:c.1 ASC-Binding Building Use

© Fretwell-Downing Informatics