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Peloruside A enhances apoptosis in H-ras-transformed cells and is cytotoxic to proliferating T cells
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Peloruside A enhances apoptosis in H-ras-transformed cells and is cytotoxic to proliferating T cells
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Journal Article
Peloruside A enhances apoptosis in H-ras-transformed cells and is cytotoxic to proliferating T cells
2004
Overview
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 microM 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 microM peloruside following 12 hours of exposure. Peloruside inhibited T cell proliferation and IL-2 and IFN gamma 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.
Publisher
Springer Nature B.V
Subject
/ Bridged Bicyclo Compounds, Heterocyclic - pharmacology
/ Cell Proliferation - drug effects
/ Cell Transformation, Neoplastic
/ Cross-Linking Reagents - pharmacology
/ Enzyme-Linked Immunosorbent Assay
/ Humans
/ Interferon-gamma - antagonists & inhibitors
/ Interleukin-2 - antagonists & inhibitors
/ Iodides
/ Lymphocyte Culture Test, Mixed
/ Mice
/ Mycale
