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.
Hubeek
I
I
Department of Pediatric Hematology/Oncology, VU University Medical Center, Amsterdam, The Netherlands. isabelle.hubeek@vumc.nl
Peters
G J
GJ
Broekhuizen
A J F
AJ
Kaspers
G J L
GJ
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D017338:Cladribine / Q000494:pharmacology; D004396:Coloring Agents / Q000494:pharmacology; D003561:Cytarabine / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D009705:Nucleosides / Q000737:chemistry*; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D004396:Coloring Agents; D009705:Nucleosides; D013778:Tetrazolium Salts; D013844:Thiazoles; D003561:Cytarabine; D003841:Deoxycytidine; D017338:Cladribine; D004247:DNA; C022616:thiazolyl blue; D014740:Vidarabine; C024352:fludarabine; D000093542:Gemcitabine