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 quantifated 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. Conclusion: Cell cycle phase perturbations appear to be suitable, early markers for cytotoxic drug efficacy