2024-03-28T21:06:38Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1221112020-08-12T12:03:30Zcom_10261_41com_10261_1col_10261_294
http://hdl.handle.net/10261/122111
10.1158/1535-7163.MCT-08-0420
301035
Mithramycin SK modulates polyploidy and cell death in colon carcinoma cells
American Association for Cancer Research
2008
artículo
Bataller, Marc
Méndez, Carmen
Salas, José A.
Portugal, José
rp13782
2008
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 G1 phase followed by the overtaking of the G2-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 G2-M through early p53-independent apoptosis, which appeared to be mediated by caspase-2, although secondary necrosis was also observed. Copyright © 2008 American Association for Cancer Research.
Generalitat de Catalunya
Red Temática de Investigación Cooperativa en Cáncer (España)
European Commission
Ministerio de Educación y Ciencia (España)
Molecular Cancer Therapeutics
2008
7
2988
2997