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Accumulation of HL-60 leukemia cells in G2/M and inhibition of cytokinesis caused by two marine compounds, bistratene A and cycloxazoline

  • Original Articles
  • Marine Compounds, Cell Cycle, Multinucleation
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Abstract

The effects on the cell cycle of two biologically active compounds, bistratene A and cycloxazoline, from the marine ascidianLissoclinum bistratum were studied in HL-60 human leukemia cells using flow cytometry. Both compounds were shown to cause an apparent accumulation of cells in the G2/M phase. This effect was shown to be both time- and dose-dependent. At the longer time points (30 and 48 h after addition of the compounds) polyploidy was apparent. The fate of cells labeled in the S phase with 5-bromo-2′-deoxyuridine (BrdUrd) was analysed using a bivariate BrdUrd/PI (propidium iodide) technique. Bistratene A and cycloxazoline treatment prevented the majority of BrdUrd-labeled cells from progressing through to the G1 phase. Approximately 50% of the cells were delayed at G2/M, and a significant proportion of cells appeared to be polyploid. Light and electron microscopy revealed the presence of multinucleated cells accounting for the apparent polyploidy. The progression of cells out of the G1 phase was also examined by synchronising cells with mimosine and releasing them from mimosine block in the presence of bistratene A. There was no evidence of a block at the G1/S phase transition or through the S phase since DNA synthesis was not inhibited. The mechanism by which these compounds interfere with cytokinesis is presently unknown but, in the case of bistratene A, may be linked to altered phosphorylation of cellular proteins involved in cell-cycle control.

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Authors and Affiliations

  1. Queensland Cancer Fund Research Unit, Queensland Institute of Medical Research, The Bancroft Centre, 300 Herston Road, Herston, 4029, Brisbane, Australia

    Diane J. Watters, Heather J. Beamish, Karen A. Marshall & Martin F. Lavin

  2. Department of Surgery, University of Queensland, Herston, 4029, Brisbane, Australia

    Robert A. Gardiner

  3. Department of Dentistry, University of Queensland, St. Lucia, 4072, Brisbane, Australia

    Gregory J. Seymour

Authors
  1. Diane J. Watters
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  2. Heather J. Beamish
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  3. Karen A. Marshall
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  4. Robert A. Gardiner
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  5. Gregory J. Seymour
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  6. Martin F. Lavin
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This paper is dedicated to the memory of Karen Marshall, who died tragically in a car accident during the course of this study

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Watters, D.J., Beamish, H.J., Marshall, K.A. et al. Accumulation of HL-60 leukemia cells in G2/M and inhibition of cytokinesis caused by two marine compounds, bistratene A and cycloxazoline. Cancer Chemother. Pharmacol. 33, 399–409 (1994). https://doi.org/10.1007/BF00686269

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  • DOI: https://doi.org/10.1007/BF00686269

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