Cdc2 and Cdk2 play critical roles in low dose doxorubicin-induced cell death through mitotic catastrophe but not in high dose doxorubicin-induced apoptosis

Park, Seok Soon; Eom, Young-Woo; Choi, Kyeong Sook

doi:10.1016/j.bbrc.2005.06.192

Cited by 41 publications

(32 citation statements)

References 25 publications

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“…19,26 On one hand, this is intrinsically linked to the propensity of p53-incompetent cancer cells to become hyperploid and genomically instable. 12,27,28 On the other hand, a transient exposure to DNA damaging agents such as anthracyclines appears to kill TP53 -/-cells more efficiently than their WT counterparts, 29,30 most likely due to the fact that absent cell cycle arrest coupled to DNA damage culminates in the activation of mitotic catastrophe, i.e., an oncosuppressive mechanism that specifically eliminates mitosisincompetent cells. 31 The checkpoint kinase 1 (Chk1) inhibitor 7-hydroxystaurosporine (UCN-01) also abrogates DNA damageinduced cell cycle arrest and triggers mitotic catastrophe preferentially in p53-deficient cancer cells.…”

Section: Resultsmentioning

confidence: 99%

Preferential killing of p53-deficient cancer cells by reversine

et al. 2012

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Section: Resultsmentioning

confidence: 99%

Preferential killing of p53-deficient cancer cells by reversine

et al. 2012

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“…However, in our previous study we observed the occurrence of cells not only with apoptotic features, but those characteristic of mitotic catastrophe (6). Several lines of evidence have indicated that high doses of DOX cause cell death via apoptosis whereas low concentrations lead to mitotic catastrophe (MC) and/or senescence (7,8). The definition of MC is still the subject of debate.…”

Section: Introductionmentioning

confidence: 99%

Actin reorganization in CHO AA8 cells undergoing mitotic catastrophe and apoptosis induced by doxorubicin

Grzanka¹

2010

Oncol Rep

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Abstract. Doxorubicin (DOX) is a drug widely used in cancer chemotherapy. Although it has been proven that DOX kills tumor cells, the triggered modes of cell death are not fully understood. There is some evidence that, depending on the dose of DOX, the treated cells undergo senescence, mitotic catastrophe, apoptosis or necrosis. The aim of this study was to assess the type of CHO AA8 cell death induced with different DOX doses. In this context, we also assessed organization and distribution of F-actin, which integrity was suggested to be indispensable for apoptosis. Following treatment with 0.5 and 1 μM DOX, the giant multinucleated cells with extended network of fine microfilaments appeared. Notably, in the nuclei of the enlarged cells microscopy and cytometric analysis showed the presence of F-actin. DOX (2.5 μM) caused the appearance of the giant cells and with apoptotic features and signs of autophagy vacuolization. Flow cytometric studies indicated a dose-dependent increase in the number of TUNELpositive cells and cells stained with both Annexin V and PI. Cell cycle analysis revealed the increase in the hyperploid DNA content. Our results suggest that treatment of CHO AA8 cells with different DOX doses caused mitotic catastrophe that was followed by apoptosis with signs of autophagy. The increase in F-actin content in the nuclei of the dying cells was evident. We hypothesize that in CHO AA8 cells F-actin may be involved in chromatin reorganization undergoing cell death.

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“…Mitotic cell death is distinguished from apoptosis by its morphological characteristics, including the enlargement of cell mass and formation of micronuclei. Furthermore, the two modes of cell death induced by different doses of doxorubicin have distinctive biochemical characteristics, such as the involvement of stress signaling pathways and cell cycle machineries [7,10]. Treatment with sub-apoptotic doses of other chemotherapeutic drugs or c-irradiation has also been shown to induce death through mitotic catastrophe of cancer cells defective in checkpoint functions [11,12].…”

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confidence: 99%