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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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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-1\u03b1 and of p53, p21, caspase-2, and of the ataxia telangiectasia mutated (ATM) target PIDD-C.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      DCQ decreased colony forming ability and viability of all HCT116 cells to a greater extent under hypoxia than normoxia and the p21\n                      <jats:sup>-\/-<\/jats:sup>\n                      cell line was most sensitive. Cells had different HIF-1\u03b1 responses to hypoxia and\/or drug treatment. In p53\n                      <jats:sup>+\/+<\/jats:sup>\n                      , DCQ significantly inhibited the hypoxia-induced increases in HIF-1\u03b1 protein, in contrast to the absence of a significant HIF-1\u03b1 increase or modulation by DCQ in p21\n                      <jats:sup>-\/-<\/jats:sup>\n                      cells. In p53\n                      <jats:sup>-\/-<\/jats:sup>\n                      cells, 10 \u03bcM DCQ significantly reduced HIF-1\u03b1 expression, especially under hypoxia, despite the constitutive expression of this protein in control cells. Higher DCQ doses induced PreG\n                      <jats:sub>1<\/jats:sub>\n                      -phase increase and apoptosis, however, lower doses caused mitotic catastrophe. In p53\n                      <jats:sup>+\/+<\/jats:sup>\n                      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\n                      <jats:sup>+\/+<\/jats:sup>\n                      cells to DCQ induced single strand breaks and triggered the activation of the nuclear kinase ATM by phosphorylation at Ser-1981 in all cell cycle phases. On the other hand, no drug toxicity to normal FHs74 Int human intestinal cell line was observed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Collectively, our findings indicate that DCQ reduces the colony survival of HCT116 and induces apoptosis even in cells that are null for p53 or p21, which makes it a molecule of clinical significance, since many resistant colon tumors harbor mutations in p53.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/1748-717x-5-107","type":"journal-article","created":{"date-parts":[[2010,11,16]],"date-time":"2010-11-16T02:16:28Z","timestamp":1289873788000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Cell death by the quinoxaline dioxide DCQ in human colon cancer cells is enhanced under hypoxia and is independent of p53 and p21"],"prefix":"10.1186","volume":"5","author":[{"given":"Mona","family":"El-Khatib","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fady","family":"Geara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makhluf J","family":"Haddadin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hala","family":"Gali-Muhtasib","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2010,11,15]]},"reference":[{"key":"313_CR1","first-page":"297","volume":"435","author":"JM Brown","year":"2007","unstructured":"Brown JM: Tumor hypoxia in cancer therapy. 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