Bryostatins trigger human polymorphonuclear neutrophil and monocyte oxidative metabolism: association with in vitro antineoplastic activity

A. H. Esa, J. T. Warren, A. D. Hess, W. S. May

Research output: Contribution to journalArticlepeer-review

Abstract

Bryostatin-1 - but not bryostatin-13 - a macrocyclic lactone isolated from the marine bryozoan Bugula neritina, triggered human polymorphonuclear neutrophil (PMN) and monocyte release of reactive oxygen radicals, as measured by the generation of lucigenin chemiluminescence and by the ferricytochrome c reduction assay. The release of oxygen radicals by bryostatins was sensitive to inhibitors of protein kinases, but resistant to the inhibition of phospholipase A2 activity and arachidonic acid metabolism (prior treatment with mepacrine or indomethacin). Comparison of the effect of protein kinase (PK) inhibitors H-8, H-7 and staurosporine on bryostatin-1-induced neutrophil oxygen radical release further suggested a requirement for activation of phospholipid-dependent PKC, but not for cGMP- or cAMP-dependent PK. In cytostatic assays, PMNs treated with bryostatin-1 inhibited the growth of the erythroleukaemic cell line K562 in a concentration-dependent manner. These findings suggest that the reported antineoplastic effect of bryostatins may result, at least in part, from activation of PMNs and monocytes.

Original languageEnglish (US)
Pages (from-to)351-361
Number of pages11
JournalResearch in Immunology
Volume146
Issue number6
DOIs
StatePublished - 1995
Externally publishedYes

Keywords

  • Bryostatin, Oxygen, Cytostasis, Polymorphonuclear leukocyte
  • Reactive oxygen radicals, Tumoricidal effect, Protein Kinase, Monocytes

ASJC Scopus subject areas

  • Immunology

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