Inhibition by Bryostatin 1 of the Phorbol Ester-induced Blockage of Differentiation in Hexamethylene Bisacetamide-treated Friend Erythroleukemia Cells

M. L. Dell'Aquila, H. T. Nguyen, C. L. Herald, George Pettit, P. M. Blumberg

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

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 HL40 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.

Original languageEnglish (US)
Pages (from-to)6006-6009
Number of pages4
JournalCancer Research
Volume47
Issue number22
StatePublished - Jan 1 1987

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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