Inhibition by bryostatin 1 of the phorbol ester-induced blockage of differentiation in hexamethylene bisacetamide-treated Friend erythroleukemia cells.
Phorbol esters inhibit chemically induced differentiation in Friend erythroleukemia cells. This study examines the effect of the macrocyclic lactone bryostatin 1 on phorbol ester responses in a Friend erythroleukemia cell clone, PS 7. In several biological systems, bryostatin 1 was reported to mimic phorbol ester action, including activation of protein kinase C, but in HL-60 cells it blocked phorbol ester-induced differentiation. We report here that bryostatin 1 blocks phorbol ester action in Friend cells (clone PS 7), a second differentiating system. In this system, in contrast to HL-60 cells, the phorbol esters inhibit rather than induce differentiation. Bryostatin 1 restores the differentiation response [50% effective dose, 15 +/- 3.5 nM (SEM)] as well as blocks a second phorbol ester effect, induction of cellular adherence. The inhibition of erythroid differentiation by dexamethasone, a nonphorbol compound whose action presumably is not protein kinase C mediated, is unaffected by bryostatin 1. Although bryostatin 1 inhibits [3H]phorbol 12,13-dibutyrate binding in intact Friend erythroleukemia cell clone PS 7, the mechanism for the antagonism of phorbol ester action by bryostatin 1 in Friend cells cannot be explained by simple competition at the binding site.
D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D054713:Bryostatins; D002273:Carcinogens / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D007700:Kinetics; D007783:Lactones / Q000494:pharmacology*; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology; D007942:Leukemia, Experimental / Q000473:pathology*; D018942:Macrolides; D051379:Mice; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D000081:Acetamides; D000970:Antineoplastic Agents; D054713:Bryostatins; D002273:Carcinogens; D007783:Lactones; D018942:Macrolides; D010703:Phorbol Esters; D015240:Phorbol 12,13-Dibutyrate; C046785:bryostatin 1; C014026:hexamethylene bisacetamide