Effects of fludarabine and gemcitabine on human acute myeloid leukemia cell line HL 60

Direct comparison of cytotoxicity and cellular Ara-C uptake enhancement

Valeria Santini, Gianluca D'Ippolito, Pietro Antonio Bernabei, Antonella Zoccolante, Angela Ermini, Pierluigi Rossi-Ferrini

Research output: Contribution to journalArticle

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Abstract

This study was designed to compare the effects of fludarabine and gemcitabine on cytosine arabinoside (Ara-C) uptake and retention, and their specific cytotoxicity on HL 60 human acute myeloid leukemia cells. The leukemic blasts were exposed to either drug at equimolar concentrations (10 μM) for 3 h and further incubated with Ara-C (5 μM), added immediately (day 0) or after an interval of 24 h in which cells were kept in a drug-free medium (day 1). On day 0, leukemic cells exposed to fludarabine 10 μM had a significant (P < 0.01) increase in Ara-C uptake (297 ± 11 pmol/107 cells) with respect to control cells (not pre-treated: 195 ± 10 pmol/107 cells). After treatment of leukemic cells with fludarabine, cytoplasmic Ara-C peaked after 180 min of exposure, as well as nuclear bound Ara-C. At the same time, a significant decrease in the number of S-phase leukemic cells, consistent with depressed [3H]TdR uptake was observed. Although on day 0 gemcitabine 10 μM did not have potentiating effects on Ara-C uptake, it showed a high degree of intrinsic cytotoxicity as a single agent (clear from cell cycle distribution, [3H]TdR uptake, plating efficiency (PE) data and percentage of apoptotic cells). Cells exposed to gemcitabine, on the other hand, showed on day 1 a significant increase in Ara-C uptake (2.4 x control values in the cytoplasmic and 3 x in the nuclear fractions) and a reduced number of S-phase blasts, [3H]TdR uptake and PEs, as well as an increased apoptotic cell death. Evidently, it is possible to modulate Ara-C uptake by leukemic cells with gemcitabine. Although this effect is similar to that demonstrated with fludarabine, its kinetics and time of efficacy are different and also, because of its intrinsic higher cytotoxicity and lack of important side effects, gemcitabine could be considered a suitable candidate for Ara-C association therapy in acute leukemia.

Original languageEnglish
Pages (from-to)37-45
Number of pages9
JournalLeukemia Research
Volume20
Issue number1
DOIs
StatePublished - Jan 1 1996
Externally publishedYes

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gemcitabine
Cytarabine
Myeloid Cells
Acute Myeloid Leukemia
Cell Line
S Phase
fludarabine

Keywords

  • Acute leukemia
  • Apoptosis
  • Arabinosylcytosine
  • Cell cycle
  • Fludarabine
  • Gemcitabine

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

Cite this

Effects of fludarabine and gemcitabine on human acute myeloid leukemia cell line HL 60 : Direct comparison of cytotoxicity and cellular Ara-C uptake enhancement. / Santini, Valeria; D'Ippolito, Gianluca; Bernabei, Pietro Antonio; Zoccolante, Antonella; Ermini, Angela; Rossi-Ferrini, Pierluigi.

In: Leukemia Research, Vol. 20, No. 1, 01.01.1996, p. 37-45.

Research output: Contribution to journalArticle

Santini, Valeria ; D'Ippolito, Gianluca ; Bernabei, Pietro Antonio ; Zoccolante, Antonella ; Ermini, Angela ; Rossi-Ferrini, Pierluigi. / Effects of fludarabine and gemcitabine on human acute myeloid leukemia cell line HL 60 : Direct comparison of cytotoxicity and cellular Ara-C uptake enhancement. In: Leukemia Research. 1996 ; Vol. 20, No. 1. pp. 37-45.
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