Modulation of cytarabine induced cytotoxicity using novel deoxynucleoside analogs in the HL60 cell line

In order to enhance the cytotoxicity of ara-C in the HL60 cell line the following deoxynucleoside analogs were used: cladribine, fludarabine and gemcitabine. HL60 cells were co-incubated with ara-C and each of the modulators at the ratios of their respective IC50s. Cytotoxicity was determined with the MTT-assay and drug interactions were evaluated with the combination index (CI) method (Calcusyn; Chou & Talalay). CI < 1, CI +/- 1 and >1 indicate synergism, additive effect and antagonism, respectively. We observed moderate synergism between ara-C/cladribine and ara-C/ gemcitabine, with CIs of 0.76 +/- 0.14 and 0.82 +/- 0.04, respectively. The interaction between ara-C/fludarabine resulted in moderate antagonism (CI = 1.29 +/- 0.11). In conclusion, in this in vitro study we showed that the cytotoxicity of ara-C can be succesfully modulated in the HL60 cell line by cladribine and gemcitabine.