The differentiation inducing effect of bryostatin 5 on human myeloid blast cells is potentiated by vitamin D3
Autor: | K G, van der Hem, A M, Dräger, P C, Huijgens, C, Tol, W, Devillé, M M, Langenhuijsen |
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Rok vydání: | 1994 |
Předmět: |
Adult
Male Adolescent Macrophages Lipopolysaccharide Receptors Antigens Differentiation Myelomonocytic Antigens CD34 Antineoplastic Agents Cell Differentiation Drug Synergism Middle Aged Bryostatins Enzyme Activation Lactones Leukemia Myeloid Acute Antigens CD Tumor Cells Cultured Humans Female Macrolides Carboxylic Ester Hydrolases Protein Kinase C Aged Cholecalciferol |
Zdroj: | Leukemia. 8(2) |
ISSN: | 0887-6924 |
Popis: | 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. |
Databáze: | OpenAIRE |
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