Bryostatin 1 activates protein kinase C and induces monocytic differentiation of HL-60 cells

R. M. Stone, E. Sariban, George Pettit, D. W. Kufe

Research output: Contribution to journalArticle

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Abstract

Phorbol esters induced the human HL-60 promyelocytic cell line to differentiate along a monocytic pathway. This induction of differentiation may involve phorbol ester-induced activation of the phospholipid- and calcium-dependent protein kinase C. Bryostatin 1, a macrocyclic lactone, has been shown to compete with phorbol esters for binding to protein kinase C. We have confirmed that bryostatin 1 translocates activity of protein kinase C from the cytosolic to membrane fractions of HL-60 cells. The present results also demonstrate that bryostatin 1 (10 nmol/L) induces monocytic differentiation of HL-60 cells as determined by adherence, growth inhibition, appearance of monocyte cell surface antigens, and α-naphthyl acetate esterase staining. Furthermore, bryostatin 1 (10 nmol/L) downregulated c-myc expression and induced c-fos, c-fms, and tumor necrosis factor transcripts. These changes in gene expression induced by bryostatin 1 are similar to those associated with phorbol ester-induced monocytic differentiation of HL-60 cells. In contrast, exposure to a higher concentration of bryostatin 1 (100 nmol/L) had less of an effect on growth inhibition of HL-60 cells and changes in gene expression. Moreover, 100 nmol/L bryostatin 1 antagonized the cytostatic effects and adherence induced by phorbol esters. Our results thus suggest that bryostatin 1 activates HL-60 cell protein kinase C and that this effect is associated with induction of monocytic differentiation.

Original languageEnglish (US)
Pages (from-to)208-213
Number of pages6
JournalBlood
Volume72
Issue number1
StatePublished - 1988
Externally publishedYes

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HL-60 Cells
Protein Kinase C
Phorbol Esters
Gene expression
Acetylesterase
Gene Expression
bryostatin 1
Phospholipids
Cytostatic Agents
Lactones
Surface Antigens
Growth
Monocytes
Calcium
Down-Regulation
Tumor Necrosis Factor-alpha
Chemical activation
Cells
Staining and Labeling
Membranes

ASJC Scopus subject areas

  • Hematology

Cite this

Bryostatin 1 activates protein kinase C and induces monocytic differentiation of HL-60 cells. / Stone, R. M.; Sariban, E.; Pettit, George; Kufe, D. W.

In: Blood, Vol. 72, No. 1, 1988, p. 208-213.

Research output: Contribution to journalArticle

Stone, RM, Sariban, E, Pettit, G & Kufe, DW 1988, 'Bryostatin 1 activates protein kinase C and induces monocytic differentiation of HL-60 cells', Blood, vol. 72, no. 1, pp. 208-213.
Stone, R. M. ; Sariban, E. ; Pettit, George ; Kufe, D. W. / Bryostatin 1 activates protein kinase C and induces monocytic differentiation of HL-60 cells. In: Blood. 1988 ; Vol. 72, No. 1. pp. 208-213.
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