| Title | Mithramycin SK modulates polyploidy and cell death in colon carcinoma cells. | | Author(s) | Bataller M, Méndez C, Salas JA, Portugal J | | Institution | Instituto de Biología Molecular de Barcelona, CSIC, Parc Cientific de Barcelona, Baldiri Reixach, 10, E-08028 Barcelona, Spain. jpmbmc@ibmb.csic.es. | | Source | Mol Cancer Ther 2008 Sep; 7(9):2988-97. | | Abstract | During a normal cell cycle, polyploidy and aneuploidy can be prevented by several checkpoints, which are mainly p53 dependent. Here, we show that treatment of HCT-116 (p53(+/+)) colon carcinoma cells with the novel antitumor antibiotic mithramycin SK (MSK) results in polyploidization and mitotic catastrophe, which occurs after a transient halt in G(1) phase followed by the overtaking of the G(2)-M checkpoint when treated cells are incubated in a fresh drug-free medium. Cells reentering aberrant mitosis mainly died by necrosis, although active caspase-3 was observed. Our results indicate that a decrease in p53 RNA and protein levels, together with concomitant changes in the expression of other proteins such as p21(WAF1), were involved in MSK-induced polyploidy. Furthermore, the effects of MSK on HCT-116 (p53(+/+)) cells cannot be attributed exclusively to the down-regulation of p53 by MSK, because these effects differed from those observed in MSK-treated HCT-116 (p53(-/-)) cells. The p53(-/-) cells died mainly from G(2)-M through early p53-independent apoptosis, which appeared to be mediated by caspase-2, although secondary necrosis was also observed. [Mol Cancer Ther 2008;7(9):2988-97]. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 18790779 |
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