title: Apoptotic-like death occurs through a caspase-independent route in colon carcinoma cells undergoing mitotic catastrophe.
abstract: We have examined the relationship between chemotherapy-induced mitotic catastrophe and cell death by apoptosis in both wild-type and p53(-/-) HCT116 human colon carcinoma cells treated with nanomolar concentrations of paclitaxel (PTX), a drug that acts on tubulin altering the normal development of mitosis. After treatment, HCT116 cells entered mitosis regardless of the presence of functional p53, which resulted in changes in the distribution of cells in the different phases of the cell cycle, and in cell death. In the presence of PTX, the percentage of polyploid cells observed was higher in p53-deficient cells, indicating that mitotic slippage was favored compared to wild-type cells, with the presence of large multinucleate cells. PTX caused mitotic catastrophe and about 50-60% cells that were entering an aberrant mitosis died through an apoptotic-like pathway characterized by the presence of phosphatidylserine in the outer cell membrane, which occurred in the absence of significant activation of caspases. Lack of p53 facilitated endoreduplication and polyploidy in PTX-treated cells, but cells were still killed with similar efficacy through the same apoptotic-like mechanism in the absence of caspase activity.
authors.affiliation: Instituto de Biologia Molecular de Barcelona, CSIC, Parc Cientific de Barcelona, Barcelona, Spain.
authors.forename: Laia
authors.initials: L
authors.lastname: Llovera
authors.forename: Sylvia
authors.initials: S
authors.lastname: Mansilla
authors.forename: José
authors.initials: J
authors.lastname: Portugal
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D020169:Caspases / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics; D016923:Cell Death / Q000235:genetics; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics*; D062951:Endoreduplication; D045325:HCT116 Cells; D006801:Humans; D008938:Mitosis; D017239:Paclitaxel / Q000494:pharmacology* / Q000627:therapeutic use; D011123:Polyploidy; D050257:Tubulin Modulators / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D050257:Tubulin Modulators; D016159:Tumor Suppressor Protein p53; D020169:Caspases; D017239:Paclitaxel