The term mitotic catastrophe has recently become widely used to describe a form of death affecting many cancer cells, which, because of severe DNA or mitotic spindle damage, are not able to bypass mitosis. We show here that cells of the HL-60-derived HCW-2 line highly resistant to apoptosis, upon treatment with curcumin or vincristine, undergo mitotic catastrophe that is finalized by caspase 3 activation and oligonucleosomal DNA degradation. Curcumin is a natural dye, derived from Curcuma longa that has been shown to induce cell death in many cancer cells. Both treatments decrease cell proliferation and cell survival, arrest cells in G2/M phase of cell cycle and induce morphological changes characterized by cell enlargement and micronucleation. "Catastrophic" cells comprise a separate subpopulation with less than 4C DNA, as evidenced by flow and scanning cytometry. This subpopulation is MPM-2 positive. Thymidine block increased the number of cell arrested in the G2/M phase of cell cycle and curcumin effectiveness as an inducer of mitotic catastrophe. Curcumin, but not vincristine, acts on HCW-2 cells by inhibiting the expression of survivin, a modulator of cell division and apoptosis in cancer. Altogether our results show that apoptosis resistance can be overcome by inducing mitotic catastrophe in HCW-2 cells.
Copyright 2006 Wiley-Liss, Inc.