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Apoptosis

, Volume 9, Issue 6, pp 785–796 | Cite as

Peloruside A enhances apoptosis in H-ras-transformed cells and is cytotoxic to proliferating T cells

  • J. H. Miller
  • B. Rouwé
  • T. N. Gaitanos
  • K. A. Hood
  • K. P. Crume
  • B. T. Bäckström
  • A. C. La Flamme
  • M. V. Berridge
  • P. T. Northcote
Article

Abstract

Peloruside A (peloruside), a compound isolated from the marine sponge Mycale hentscheli, inhibits growth of human (HL-60) and mouse (32D-ras) myeloid leukemic cells, as well as non-transformed 32D cells. Using the MTT cell proliferation assay and trypan blue dye exclusion tests, little difference was seen in growth inhibition between 32D and 32D-ras cells; however, peloruside was more cytotoxic to the oncogene-transformed cells. Peloruside also blocked 32D-ras cells more readily in G2/M of the cell cycle, leading to apoptosis. Annexin-V/propidium iodide staining of 32D and 32D-ras cells showed that 1.6 μM peloruside induced significant cell death by 36 hours in 32D cells (16% survival), but to comparable levels as early as 14 hours in 32D-ras cells (11% survival). There was no evidence for activation of either of the initiator caspases-8 or -9 by 0.1 μM peloruside following 12 hours of exposure. Peloruside inhibited T cell proliferation and IL-2 and IFN γ production in both the mixed lymphocyte reaction and following CD3 cross-linking, and this effect was shown to be a non-specific cytotoxic effect. It is concluded that peloruside preferentially targets oncogene-transformed cells over non-transformed cells by inducing transformed cells to undergo apoptosis.

caspase immunosuppression mycalamide pateamine peloruside Ras 

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Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • J. H. Miller
    • 1
  • B. Rouwé
    • 1
  • T. N. Gaitanos
    • 1
  • K. A. Hood
    • 1
  • K. P. Crume
    • 1
  • B. T. Bäckström
    • 2
  • A. C. La Flamme
    • 1
  • M. V. Berridge
    • 2
  • P. T. Northcote
    • 3
  1. 1.School of Biological SciencesVictoria University of WellingtonWellingtonNew Zealand
  2. 2.Malaghan Institute of Medical ResearchWellington SouthNew Zealand
  3. 3.School of Chemical and Physical SciencesVictoria University of WellingtonWellingtonNew Zealand

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