Mechanisms of Drug-Induced Mitotic Catastrophe in Cancer Cells

Apoptotic-like death occurs through a caspase-independent route in colon carcinoma cells undergoing mitotic catastrophe

“…Here, we have demonstrated that these pathways are operative in HCT116 human colon carcinoma cells upon PTX treatment, in keeping with the view that they may depend in drug doses and cell types [9][10][11]. Although it has been previously reported that mitotic catastrophe can result in cell death by caspase-independent mechanisms (reviewed in [15]), our results peculiarly show cells that were killed by apoptosis rather than by necrosis. In the absence of direct evidence about the mechanisms and molecules involved in the apoptotic cell death that is working under our experimental conditions, it is clear that alternative protease activities must be capable of inducing apoptotic-like death [36].…”

“…Although apoptosis can follow a faulty mitosis, mitotic catastrophe has been regarded as fundamentally different from apoptosis [1,14] mainly because the overexpression of several antiapoptotic genes enhances the frequency of defective mitosis [1,15]. This has raised the question of whether the large multinucleate cells that emerge after a faulty mitosis may become more invasive.…”

Harnessing the complexity of DNA-damage response pathways to improve cancer treatment outcomes

“…Mitotic catastrophe is an abnormal mitosis that is characterized by micronucleated cells that continue with mitosis to form aneuploid cells, abort mitosis and die apoptotic or necrotic deaths, or undergo irreversible growth arrest. Thus, the term mitotic catastrophe should be restricted to faulty mitosis leading to irreversible growth arrest or cell death (by apoptosis or necrosis) (Vakifahmetoglu et al, 2008b;Kroemer et al, 2009;Portugal et al, 2009Portugal et al, , 2010.…”

Definições E Mecanismos Moleculares Em Morte Celular

“…É a principal forma de morte induzida por radiação ionizante nas células, e ocorre como um resultado de uma falha no início da mitose após a replicação do DNA. Esse mecanismo é diferente do mecanismo de apoptose, contudo, vários modelos in vivo e in vitro demonstraram que existe associação dos precursores de morte celular na MC, que pode ser acompanhada pela liberação de proteínas pró-apoptóticas e ativação de caspases, o que mostra que alguns eventos se assemelham entre este mecanismo e o mecanismo de apoptose (PORTUGAL et al 2010).…”

“…Esse fato ocorre na dependência da ação da p53. Já no caso de tumores sólidos, que geralmente não apresentam a p53 funcional, a via de morte celular primária após o uso de quimoterápicos lesivos ao DNA, envolve a MC (PORTUGAL et al 2010). ANOIKIS É um termo de origem grega introduzido em 1994 para descrever a resposta apoptótica de células aderentes, devido à ausência de interação entre a célula e a matriz extracelular.…”