EFFECTS OF ELLIPTICINE ON CELL-SURVIVAL AND CELL-CYCLE PROGRESSION IN CULTURED MAMMALIAN-CELLS

  • 1 January 1980
    • journal article
    • research article
    • Vol. 40  (7) , 2390-2399
Abstract
The effects of ellipticine [5,11-dimethyl-6H-pyrido(4,3-b)carbazole; NSC 71795] on cell viability, growth and colony formation were investigated in suspension using mouse Friend leukemia virus-induced cells, mouse leukemia L-1210 cells and adherent Chinese hamster ovary CHO tumor cells and in mitogen[phytohemagglutinin]-stimulated human peripheral blood lymphocyte cultures. Cell cycle progression and the terminal point of action of the drug were monitored by flow cytometry. Ellipticine was cytostatic for all cell lines tested, blocking cells in G2 phase following 24 h constant exposure at concentrations in the range of 1.0 .mu.g/ml. A 10 times higher drug concentration was required to block cells in G2 if the cells were exposed for only 30 min to the drug followed by 23.5 h culture in drug-free medium. Formation of CHO cell colonies was inhibited by 50% following exposure to ellipticine for 2 h at 6.0 .mu.g/ or for 24 h at 0.3 .mu.g/ml. Fifty percent cell kill in asynchronously growing Friend leukemia and L-1210 cells was obtained following exposure to ellipticine for 24 h at 2.0 .mu.g/ml and 1.15 .mu.g/ml, respectively; human peripheral blood lymphocytes required 66 h exposure to 1.0 .mu.g/ml to kill 50% of the cells. Phytohemagglutinin-stimulated lymphocytes were remarkably resistant to the cytotoxic effect of ellipticine but did display a dose-dependent inhibition of stimulation and accumulation in G2 whether the drug was added prior to or during active cell proliferation. Ellipticine, at cytostatic concentrations, had a marked effect on cellular RNA content. Friend leukemia cells, blocked in G2 by the drug, doubled their RNA content compared to control cells. L-1210 and CHO cells, but not lymphocytes, also increased in RNA content following ellipticine treatment. Drug concentrations which blocked cells in G2 also led, in the case of Friend leukemia and L-1210 but not CHO cells to an increase in the proportion of cells with greater than 4C amounts of DNA.

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