Effect of FMdC on the cell cycle of some leukemia cell lines.

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Skierski JS, Koronkiewicz M, Grieb P

Effect of FMdC on the cell cycle of some leukemia cell lines.

Cytometry. 1999 Dec 1;37(4):302-7.

PubMed ID

10547615 [ View in PubMed

]

Abstract

BACKGROUND: (E)-2'-deoxy-2'-(fluoromethylene)-cytidine (FMdC), an irreversible inhibitor of ribonucleotide reductase, displays a strong toxicity towards many cell lines derived from human solid tumors, while its activity on leukemia lines is less well-known. The aim of this study was to assess the effect of FMdC on the cell cycle and cell death of human leukemia lines HL-60 and MOLT-4, and murine leukemia L-1210 in vitro. It has been assumed that a prerequisite of FMdC cytotoxicity is intracellular phosphorylation by deoxycytidine kinase (dCK). METHODS: Cell cultures in the exponential phase of growth were exposed to different concentrations of FMdC (10 nM to 10 microM) for 6 and 24 hours. In a parallel set of experiments 1 mM deoxycytidine was added to prevent phosphorylation of the drug by dCK. The DNA and protein content in the cells, as well as Annexin V/PI binding were assessed by flow cytometry. The cell cycle was analyzed by the MacCycle software. RESULTS: The cytotoxic effects of FMdC, i.e., G(1)/S block and cell death were observed, associated with pronounced changes in the protein content. These effects were of variable intensity among the cell lines studied (HL-60 being the most susceptible), and in some cases, were not completely reversed by deoxycytidine excess. CONCLUSIONS: FMdC is a potent cytotoxic/cytostatic agent against human leukemia cell lines in vitro. It also changes the cellular protein content. Unphosphorylated FMdC may slightly influence the cell cycle of some leukemic lines.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Tezacitabine	Ribonucleoside-diphosphate reductase large subunit	Protein	Humans	Unknown	Not Available	Details