Relationship of acivicin-induced monocytoid differentiation of human myeloid leukemia cells to acivicin-induced modulation of growth factor, cytokine, and protooncogene mRNA expression release_c2igsd2mrjem5b5ry25bouecii

by J B Weinberg, S N Mason

Published in Cancer Research.

1991   Volume 51, Issue 4, p1202-9

Abstract

We have previously noted that the glutamine antagonist acivicin (alpha S,5S-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid) induces monocytoid differentiation of freshly isolated human myeloid leukemia cells and HL-60 cells. This study was designed to determine the effects of acivicin on the levels of HL-60 cell mRNA transcripts of several cytokines, growth factors, and protooncogenes implicated in the control of hematopoietic cell proliferation and differentiation. Control HL-60 cells did not express mRNA for granulocyte-colony-stimulating factor, granulocyte-macrophage-colony-stimulating factor, interleukin 3, or interleukin 6, and acivicin or phorbol myristate acetate did not induce their expression. Phorbol myristate acetate reduced expression of c-myc, c-myb, and heat shock protein 70 and enhanced those of macrophage-colony-stimulating factor and c-fms. Acivicin caused a decreased expression of c-myc, and an increased expression of mRNA for interleukin 1 beta and tumor necrosis factor alpha (TNF-alpha). The drug also caused an initial increase in c-myb, followed by a subsequent decrease below baseline levels. Supernatants and lysates of acivicin-treated HL-60 cells contained increased levels of interleukin 1 beta. Both TNF-alpha and interleukin 1 beta have been shown previously to influence hematopoietic cell differentiation. In our experiments, exogenous interleukin 1 added to HL-60 cells did not induce differentiation, but the combination of interleukin 1 and TNF synergistically enhanced the process. Pretreatment of the cells with TNF enhanced their responsiveness to subsequent treatment with interleukin 1. Our results demonstrate that the glutamine antagonist acivicin modulates HL-60 cell expression of TNF-alpha, interleukin 1 beta, c-myc, and c-myb and suggest that interleukin 1 beta and TNF-alpha might (in an autocrine manner) cause the differentiation.
In text/plain format

Archived Files and Locations

application/pdf  1.7 MB
file_sw4r5i3b4jenppy6llhmeiisxm
cancerres.aacrjournals.org (web)
web.archive.org (webarchive)
application/pdf  1.7 MB
file_2dd4f2cgwbh6nj3joflitxfxra
cancerres.aacrjournals.org (web)
web.archive.org (webarchive)
Read Archived PDF
Preserved and Accessible
Type  article-journal
Stage   published
Date   1991-02-15
Language   en ?
PubMed  1997162
Container Metadata
Not in DOAJ
In Keepers Registry
ISSN-L:  0008-5472
Work Entity
access all versions, variants, and formats of this works (eg, pre-prints)
Catalog Record
Revision: eb1cdb34-82c6-42bf-a848-1df3d13e2e5e
API URL: JSON