TY - JOUR
T1 - Bryostatins trigger human polymorphonuclear neutrophil and monocyte oxidative metabolism
T2 - association with in vitro antineoplastic activity
AU - Esa, A. H.
AU - Warren, J. T.
AU - Hess, A. D.
AU - May, W. S.
N1 - Funding Information:
This work was supported in part by NIH Grants AI24682 and CA15396 and American Cancer Society grant IM398.
PY - 1995
Y1 - 1995
N2 - 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.
AB - 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.
KW - Bryostatin, Oxygen, Cytostasis, Polymorphonuclear leukocyte
KW - Reactive oxygen radicals, Tumoricidal effect, Protein Kinase, Monocytes
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U2 - 10.1016/0923-2494(96)81039-X
DO - 10.1016/0923-2494(96)81039-X
M3 - Article
C2 - 8719659
AN - SCOPUS:0028866320
VL - 146
SP - 351
EP - 361
JO - Research in Immunology
JF - Research in Immunology
SN - 0923-2494
IS - 6
ER -