The differentiation inducing effect of bryostatin 5 on human myeloid blast cells is potentiated by vitamin D3
van der Hem, K.G.; Dräger, A.M.; Huijgens, P.C.; Tol, C.; Devillé, W.; Langenhuijsen, M.M.
Leukemia 8(2): 266-273
1994
ISSN/ISBN: 0887-6924 PMID: 7508534 Document Number: 425845
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 D-3. 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 D-3. CD14 expression was significantly (p = 0.035) enhanced with the combination of bryostatin 5 and vitamin D-3. 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 D-3, 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 VD-3 has an additional effect. These findings strengthen the potential role of bryostatins as possible antileukemic agents.