Resistance to apoptosis of HCW-2 cells can be overcome by curcumin- or vincristine-induced mitotic catastrophe.
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.
Magalska
Adriana
A
Department of Cellular Biochemistry, Nencki Institute of Experimental Biology, Warsaw, Poland.
Sliwinska
Malgorzata
M
Szczepanowska
Joanna
J
Salvioli
Stefano
S
Franceschi
Claudio
C
Sikora
Ewa
E
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology*; D004247:DNA / Q000235:genetics; D006801:Humans; D008938:Mitosis / Q000187:drug effects*; D008941:Spindle Apparatus / Q000187:drug effects; D014750:Vincristine / Q000494:pharmacology*
D014750:Vincristine; D004247:DNA; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003474:Curcumin