Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Radiation Oncology cung cấp cho các bạn kiến thức về ngành y đề tài: Cell death by the quinoxaline dioxide DCQ in human colon cancer cells is enhanced under hypoxia and is independent of p53 and p21. | El-Khatib et al. Radiation Oncology 2010 5 107 http content 5 1 107 RADIATION ONCOLOGY RESEARCH Open Access Cell death by the quinoxaline dioxide DCQ in human colon cancer cells is enhanced under hypoxia and is independent of p53 and p21 Mona El-Khatib1 Fady Geara2 Makhluf J Haddadin3 Hala Gali-Muhtasib1 Abstract Introduction We have shown that the radio sensitizer DCQ enhances sensitivity of HCT116 human colon cancer cells to hypoxia. However it is not known whether the p53 or p21 genes influence cellular response to DCQ. In this study we used HCT116 that are either wildtype for p53 and p21 null for p53 or null for p21 to understand the role of these genes in DCQ toxicity. Methods HCT116 cells were exposed to DCQ and incubated under normoxia or hypoxia and the viability colony forming ability DNA damage and apoptotic responses of these cells was determined in addition to the modulation of HIF-1a and of p53 p21 caspase-2 and of the ataxia telangiectasia mutated ATM target PIDD-C. Results DCQ decreased colony forming ability and viability of all HCT116 cells to a greater extent under hypoxia than normoxia and the p21- -cell line was most sensitive. Cells had different HIF-1a responses to hypoxia and or drug treatment. In p53 DCQ significantly inhibited the hypoxia-induced increases in HIF-1a protein in contrast to the absence of a significant HIF-1a increase or modulation by DCQ in p21- - cells. In p53- - cells 10 pM DCQ significantly reduced HIF-1a expression especially under hypoxia despite the constitutive expression of this protein in control cells. Higher DCQ doses induced PreG1-phase increase and apoptosis however lower doses caused mitotic catastrophe. In p53 cells apoptosis correlated with the increased expression of the pro-apoptotic caspase-2 and inhibition of the pro-survival protein PIDD-C. Exposure of p53 cells to DCQ induced single strand breaks and triggered the activation of the nuclear kinase ATM by phosphorylation at Ser-1981 in
