Influence of gemcitabine (2',2'-difluoro-deoxycytidine) and 2-chlorodeoxyadenosine on growth of normal and leukemic cells in vitro

Eur J Haematol. 2000 Nov;65(5):317-21. doi: 10.1034/j.1600-0609.2000.065005317.x.

Abstract

The aim of the study was to investigate the influence of gemcitabine (2',2'-difluorodeoxycytidine, dFdC) used alone and in combination with 2-chlorodeoxyadenosine (2-CdA) on the colony growth of normal granulocyte-macrophage progenitor cells (CFU-GM) from 15 hematologically healthy donors as well as on CFU-GM from 15 chronic myelogenous leukemia (CML) patients in semisolid cultures in vitro. dFdC and 2-CdA were used either separately or in the following combinations of concentrations: (1) 0.25 nM of dFdC and 2.5 nM of 2-CdA; (2) 0.5 nM of dFdC and 5 nM of 2-CdA; (3) 1 nM of dFdC and 10 nM of 2-CdA; (4) 2 nM of dFdC and 20 nM of 2-CdA. We observed that both dFdC and 2-CdA used separately inhibited the growth of colonies formed by normal and CML CFU-GM cells in a dose-dependent manner. Moreover, the combined therapy with dFdC and 2-CdA caused statistically significant inhibition of the colony growth in both normal and CML CFU-GM cultures. In addition, the inhibition of CML CFU-GM colony formation was greater and statistically significant in the case of the combined therapy using higher concentrations of these drugs as compared with inhibition of the growth of normal CFU-GM colonies. These observations were the basis for the evaluation of the interaction type between dFdC and 2-CdA. We have shown that dFdC used in a combination with 2-CdA acts in an additive way on normal and CML CFU-GM cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antimetabolites, Antineoplastic / pharmacology
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols
  • Cell Culture Techniques
  • Cell Division / drug effects
  • Cladribine / pharmacology*
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacology*
  • Dose-Response Relationship, Drug
  • Gemcitabine
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Middle Aged
  • Stem Cells / cytology
  • Stem Cells / drug effects

Substances

  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents
  • Deoxycytidine
  • Cladribine
  • Gemcitabine