American Association for Cancer Research
Browse

Supplementary Fig. S1 from Mithramycin SK modulates polyploidy and cell death in colon carcinoma cells

Download (75.54 kB)
journal contribution
posted on 2023-03-31, 23:03 authored by Marc Bataller, Carmen Méndez, José A. Salas, José Portugal
Supplementary Fig. S1 from Mithramycin SK modulates polyploidy and cell death in colon carcinoma cells

History

ARTICLE 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 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 p21WAF1, 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. [Mol Cancer Ther 2008;7(9):2988–97]