Journal article
Monocytoid Differentiation of Freshly Isolated Human Myeloid Leukemia Cells and HL-60 Cells. Induced by the Glutamine Antagonist Acivicin
Blood, Vol.74(5), pp.1728-1737
10/01/1989
DOI: 10.1182/blood.V74.5.1728.1728
PMID: 2790198
Abstract
Previously we showed that starvation of HL-60 promyelocyte leukemia cells for a single essential amino acid induced irreversible differentiation into more mature monocyte-like cells. Although not an essential amino acid, glutamine is important in the growth of normal and neoplastic cells. The glutamine analogue, α S,5S- α -amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (acivicin) inhibits several glutamine-utilizing enzymes and therefore depletes cells of certain metabolic end products. The current study was designed to examine in vitro the effects of acivicin on growth and differentiation of several established human myeloid leukemia cell lines, including the HL-60 cell line, and of freshly isolated cells from patients with acute nonlymphocytic leukemia (ANLL). Four-day culture of HL-60 cells with acivicin at concentrations of 0.1 to 10.0 Mg/mL (0.56 to 56 nmol/L) decreased cell growth by 33% to 88% as compared with untreated control cells. Viability of cells was >92% for untreated cells and 93% to 41 % for acivicin-treated cells. Cells treated with acivicin differentiated along a monocytic pathway as shown by increased H202 production and a-napthyl butyrate esterase (NSE) content. Differentiation was time and dose dependent, and was irreversible. Changes in H2O2 production and NSE content were partially abrogated by co-culture with 10 mmol/L exogenous cytidine and guanosine but not by co-culture with other nucleosides or glutamine. At these concentrations of acivicin, differentiation was associated with expression of the N-formyl-methyl-leucyl-phenylala-nine-receptor (FMLP-R) on 8% to 29% of cells as compared with 8% for control cells. Acivicin potentiated the differentiating effects of interferon-7, tumor necrosis factor, dihy-droxyvitamin D3, dimethylsulfoxide, and retinoic acid. Culture of cells from the U937 (monoblastic), K562 (erythroleukemia), and KG-1 (myeloblasts) cell lines resulted in decreased growth and viability, but not consistently in differentiation. Acivicin decreased survival of freshly isolated ANLL cells and increased their H2O2 production and NSE content. These results suggest that the glutamine analogue acivicin may be useful as a differentiating agent with antileukemia activity in patients with ANLL. © 1989 by Grune & Stratton. Inc.
Details
- Title: Subtitle
- Monocytoid Differentiation of Freshly Isolated Human Myeloid Leukemia Cells and HL-60 Cells. Induced by the Glutamine Antagonist Acivicin
- Creators
- Kim E. Nichols - Durham VA Medical CenterShobha R. Chitneni - Durham VA Medical CenterJoseph O. Moore - Durham VA Medical CenterJ. Brice Weinberg - Durham VA Medical Center
- Resource Type
- Journal article
- Publication Details
- Blood, Vol.74(5), pp.1728-1737
- Publisher
- Elsevier Inc
- DOI
- 10.1182/blood.V74.5.1728.1728
- PMID
- 2790198
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Language
- English
- Date published
- 10/01/1989
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984691557602771
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