Mitotic Catastrophe as a Consequence of Chemotherapy
According to a widespread model, anti-cancer chemotherapy involves the triggering of tumor cells to undergo apoptosis, so apoptosis-resistant cells would be recalcitrant to such therapy. However, in addition to apoptosis, which is mainly dependent on the activity of the tumor suppressor protein p53, cells can be eliminated following DNA damage by other mechanisms. Mitotic catastrophe, a form of cell death that results from abnormal mitosis, is one such mechanism. While the term mitotic catastrophe has been used to describe a type of cell death that occurs during mitosis, there is still no broadly accepted definition. Occasionally, mitotic catastrophe is used restrictively for abnormal mitosis leading to cell death, which can occur through necrosis or apoptosis, rather than cell death itself. Although different classes of cytotoxic agents induce mitotic catastrophe, the pathways of abnormal mitosis differ depending on the nature of the inducer and the status of cell-cycle checkpoints. Moreover, mitotic catastrophe can also develop because of aberrant re-entry of tumor cells into the cell cycle after prolonged growth arrest. Elucidation of the factors that regulate different aspects of treatment- induced mitotic catastrophe should assist in improving the efficacy of anti-cancer therapy, providing opportunities for the development of new drugs.
Keywords: DNA-binding drugs, mitotic catastrophe, senescence, p53, apoptosis, caspases, cyclin-dependent kinases
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