Cell cycle arrest and clonogenic tumor cell kill by divergent chemotherapeutic drugs.
BACKGROUND
Regulators of cell cycle phase transitions could be important targets for cancer treatment using cytostatic chemotherapy. Therefore, the extent of cell cycle arrest induced by different cytostatic agents has to be correlated with ultimate clonogenic tumor cell death. Especially the value of early cell cycle perturbations as indicators for the clinical efficacy of drugs should be a matter of investigation.


METHODS
In vitro PC-3 human prostate carcinoma cells were incubated for 24 hours with a panel of six different chemotherapeutic drugs in various concentrations (Aplidine, Cisplatin, Isohomohalichondrin B (IHB), Taxol, Vincristine and Vinorelbine). The short term effects on the cell cycle distribution were determined by DNA flowcytometry while the clonogenic capacity of these cells was quantitated to measure the cytotoxic treatment efficacy.


RESULTS
Significant decreases of clonogenic survival proved to be strongly correlated with cell cycle perturbations. IHB, Taxol, Vincristine and Vinorelbine resulted in accumulation (up to 87-92%) in the G2M phase, while Cisplatin and Aplidine led to increases in the S-phase fraction and in both G2M- as well as S-phase fractions, respectively.


CONCLUSIONS
Cell cycle phase perturbations appear to be suitable, early markers for cytotoxic drug efficacy.
Department of Urology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
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Mastbergen
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Duivenvoorden
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Versteegh
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Geldof
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D047630:Depsipeptides; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D010456:Peptides, Cyclic; D011714:Pyrans / Q000494:pharmacology*; D013141:Spiro Compounds / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D000970:Antineoplastic Agents; D047630:Depsipeptides; D009842:Oligopeptides; D010456:Peptides, Cyclic; D011714:Pyrans; D013141:Spiro Compounds; C099151:isohomohalichondrin B; C098980:plitidepsin