Antineoplastic bryostatins are multipotential stimulators of human hematopoietic progenitor cells.
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.
May
W S
WS
Johns Hopkins Oncology Center, Johns Hopkins University, Baltimore, MD 21205.
Sharkis
S J
SJ
Esa
A H
AH
Gebbia
V
V
Kraft
A S
AS
Pettit
G R
GR
Sensenbrenner
L L
LL
D000970:Antineoplastic Agents / Q000494:pharmacology*; D054713:Bryostatins; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D008163:Luminescent Measurements; D018942:Macrolides; D009504:Neutrophils / Q000187:drug effects
D000970:Antineoplastic Agents; D054713:Bryostatins; D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007783:Lactones; D018942:Macrolides; C046785:bryostatin 1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor