Effects of bryostatin-5 and hematopoietic growth factors on acute myeloid leukemia cell differentiation, proliferation, and primary plating efficiency.
We examined the effect of bryostatin-5 (bryo-5) with and without a combination of myeloid growth promoting factors on human acute myeloid leukemia (AML) cell growth, maturation, and primary plating efficiency. In vitro treatment of AML samples with bryo-5 induced a macrophage-like cell differentiation as evidenced by morphological changes, esterase staining, and cell surface expression of CD11a and CD18. AML cells exposed to growth factors doubled their cell numbers following culture, this increase being abrogated by co-exposure to bryo-5. An antiproliferative effect, as well as the antagonistic interaction of bryo-5 with growth factors, was confirmed in methylcellulose clonogenic assays. Together, these findings indicate that the compound bryo-5 exerts an anti-proliferative effect on AML cells and counteracts growth factor induced leukemic proliferation.
van der Hem
K G
KG
Department of Hematology, Free University Hospital, Amsterdam, The Netherlands.
Dräger
A M
AM
Odding
J H
JH
Huijgens
P C
PC
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D054713:Bryostatins; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002999:Clone Cells / Q000166:cytology; D004789:Enzyme Activation; D005260:Female; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D007783:Lactones / Q000494:pharmacology*; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D018942:Macrolides; D008264:Macrophages / Q000166:cytology; D008297:Male; D008875:Middle Aged; D011493:Protein Kinase C / Q000378:metabolism; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D000970:Antineoplastic Agents; D054713:Bryostatins; D006133:Growth Substances; D016023:Integrins; D007783:Lactones; D018942:Macrolides; C078062:bryostatin 5; D011493:Protein Kinase C