Effects of acronycine and of cytochalasin B on the division of rat leukemia cells

Abstract

Acronycine (AN) is a lipophilic antineoplastic alkaloid which, like cytochalasin B (CB), inhibits nucleoside transport and causes binucleation through interference with cell cleavage. Unlike CB, AN causes swelling of membranous organelles and does not inhibit microfilament-mediated epithelial cell contractions. The effects of AN (6–12 μg/ml) and CB (1.5–4 μg/ml) on cell division were compared by direct observation and time-lapse cinemicrography in cultured IRC 741 rat leukemia cells. Both drugs caused dose-dependent binucleation and inhibition of the normal increase in cell numbers with the effects of 12 μg/ml AN approximating those of 4 μg/ml CB. In cells entering division after exposure to the drugs for up to 24 h, furrowing was completely inhibited in a dose-dependent proportion of cells by CB but not by AN. In cells where furrowing occurred, the intervals from the onset of anaphase to furrow initiation were shortened significantly by 1.5–3 μg/ml CB, but not by 4 μg/ml CB; they were also shortened after 4/2–6 h of 12 μg/ml AN, but were prolonged up to 60% by 7–24 h of 12 μg/ml AN. Intervals from furrow initiation to daughter cell separation were prolonged up to 50% by AN and 140% by CB. The intervals from onset of anaphase to nuclear membrane reconstitution were not affected by AN for up to 18 h and lengthened thereafter; they were shortened by CB after 3–19 h, depending on the dose. In AN-treated cells, single furrows formed and cleavage was accompanied by twisting and exaggerated elongation along the long axis of the dividing cells, while CB-treated cleaving cells were characterized by surface blebbing and the formation of several consecutive incomplete furrows. Most CB effects occurred rapidly, while AN effects were delayed. The results suggest that the modes of action of CB and AN differ and support other data indicating that AN interferes primarily with the structure, function and/or turnover of cell membrane components.