The differentiation inducing effect of bryostatin 5 on human myeloid blast cells is potentiated by vitamin D3.
Bryostatin 5 is a macrocyclic lactone which activates protein kinase C (PKC). PKC activation has been implicated in leukemic cell differentiation. We have examined the effect of PKC activation by bryostatin 5 on human acute myeloid cell differentiation in the presence and absence of vitamin D3. In vitro treatment of 20 patient samples of acute myeloid leukemias in a 4 days culture system with 10 nM bryostatin 5 induced strongly adherent macrophage-like cells in all cases. Bryostatin 5 induced a significant (p = 0.00006) increment in esterase activity in a majority of the samples, which was further enhanced by vitamin D3. CD14 expression was significantly (p = 0.035) enhanced with the combination of bryostatin 5 and vitamin D3. Nitroblue tetrazolium (NBT) reducing ability was, however, nearly abolished (p = 0.0007). A loss of CD34 expression occurred during cell culture; this loss was enhanced by vitamin D3, but prevented partly by bryostatin 5. Together these findings indicate that exposure to bryostatin 5 leads to a strong macrophage-like cell differentiation in human myeloid leukemia and that VD3 has an additional effect. These findings strengthen the potential role of bryostatins as possible antileukemic agents.
van der Hem
K G
KG
Department of Hematology, Free University Hospital, Amsterdam, The Netherlands.
Dräger
A M
AM
Huijgens
P C
PC
Tol
C
C
Devillé
W
W
Langenhuijsen
M M
MM
D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D018952:Antigens, CD34; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D054713:Bryostatins; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002762:Cholecalciferol / Q000494:pharmacology*; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology / Q000276:immunology / Q000473:pathology*; D018950:Lipopolysaccharide Receptors; D018942:Macrolides; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011493:Protein Kinase C / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology / Q000473:pathology
D015703:Antigens, CD; D018952:Antigens, CD34; D015214:Antigens, Differentiation, Myelomonocytic; D000970:Antineoplastic Agents; D054713:Bryostatins; D007783:Lactones; D018950:Lipopolysaccharide Receptors; D018942:Macrolides; D002762:Cholecalciferol; C078062:bryostatin 5; D011493:Protein Kinase C; D002265:Carboxylic Ester Hydrolases; C021487:butyrylesterase