Abstract:
:The bryostatins are macrocyclic lactones, extracted from the marine bryozoan Bugula neritina, and have been reported to be potent antineoplastic agents. Results described here demonstrate that the bryostatins may also be useful as stimulators of normal human hematopoietic cells since they can (i) directly stimulate bone marrow progenitor cells to form colonies in vitro and (ii) functionally activate neutrophils. Structure-activity studies with bryostatin congeners indicate that these stimulatory properties may be dependent on the chain length and the unsaturated nature of the acylated group at carbons 20 and 7 of the bryostatin molecule. These stimulatory properties demonstrate that the naturally occurring bryostatins can mimic many of the biological effects of multipotential granulocyte-macrophage colony-stimulating factor. Thus, the coupling of antineoplastic activity with stimulatory growth properties for normal hematopoietic cells makes this agent an excellent probe to dissect the mechanism(s) of normal hematopoiesis. In addition, bryostatin may represent a clinically attractive agent useful for treating bone marrow failure states.
journal_name
Proc Natl Acad Sci U S Aauthors
May WS,Sharkis SJ,Esa AH,Gebbia V,Kraft AS,Pettit GR,Sensenbrenner LLdoi
10.1073/pnas.84.23.8483subject
Has Abstractpub_date
1987-12-01 00:00:00pages
8483-7issue
23eissn
0027-8424issn
1091-6490journal_volume
84pub_type
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