Induction of apoptosis by the anti-tubulin drug colcemid: relationship of mitotic checkpoint control to the induction of apoptosis in HeLa S3 cells.
We have studied the relationship between apoptosis and drug-induced cell cycle perturbation in HeLa S3 cells when treated with the anti-tubulin drug colcemid. We found that at least two distinct mechanisms contributed to colcemid cytotoxicity and apoptosis. Continuous exposure to concentrations of colcemid sufficient to block cells at the mitotic checkpoint led to the appearance of apoptotic cells approximately one cell cycle after their initial accumulation in mitosis. Continuous exposure to concentrations sufficient to delay mitotic progression but insufficient to cause mitotic arrest, or pulse exposure to concentrations of colcemid sufficient to induce mitotic block, led to the generation of multipolar mitoses and genetically deficient hypodiploid daughter cells which underwent apoptosis while in interphase. The fact that aberrant spindle function delayed but did not block cells at the mitotic checkpoint indicates that the mitotic checkpoint senses the presence or absence of the spindle but not spindle abnormalities. In both mitotic and interphase cells, colcemid-induced apoptosis occurred after a period of cell cycle stasis during which cells failed to complete an initiated cell cycle. These results are discussed with reference to understanding the relationship between apoptosis and the regulation of cell cycle progression.
Sherwood
S W
SW
Department of Biological Sciences, Stanford University, California 94305.
Sheridan
J P
JP
Schimke
R T
RT
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002453:Cell Cycle; D016213:Cyclins / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D003703:Demecolcine / Q000494:pharmacology*; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D007399:Interphase; D008938:Mitosis; D008941:Spindle Apparatus / Q000502:physiology; D014404:Tubulin / Q000378:metabolism; D050257:Tubulin Modulators
D016213:Cyclins; D006657:Histones; D014404:Tubulin; D050257:Tubulin Modulators; D004247:DNA; D003703:Demecolcine