Essential amino acid deprivation induces monocytic differentiation of the human HL-60 myeloid leukemia cell line.

Published

Journal Article

In this study we examine the effects of amino acid deprivation on the growth and differentiation of the human HL-60 myeloid leukemia cell line. The HL-60 cell line was chosen for study because of its ability to differentiate along either a granulocytic or monocytic pathway under appropriate culture conditions. Differentiation was determined by changes in cell morphology, nonspecific esterase (NSE) content, hydrogen peroxide (H2O2) production, and expression of the cell surface differentiation antigens LeuM3 (CD14) and OKM1 (CD11). Using a model system in which HL-60 cells were cultured in medium that selectively lacked one amino acid (AA), it was seen that deprivation of HL-60 cells for essential (but not nonessential) AAs results in decreased cell growth and viability and in differentiation of 30% to 60% of the surviving population of cells specifically along the monocytic pathway. This differentiation is irreversible as well as time- and dose-dependent. Culture of HL-60 cells in essential AA-deficient medium potentiated the differentiative effects of recombinant human interferon-gamma (IFN-gamma), recombinant human tumor necrosis factor (TNF), and dihydroxyvitamin D3 (D3), all of which have previously been shown to induce monocytic differentiation of HL-60 cells. Differentiated cells had decreased DNA and RNA synthesis, but protein synthesis was unchanged compared with control cells. The protein synthesis inhibitor cycloheximide prevented differentiation, indicating the necessity of protein synthesis in this process. Cell cycle analysis revealed that an increased proportion of cells cultured in AA-deficient medium was arrested in G0-G1 (80% and 50% for AA-deficient and control cells, respectively). These results suggest that alterations of AA metabolism and subsequent perturbations in DNA and RNA synthesis may be important in initiating differentiation or in augmenting cytokine-induced differentiation of HL-60 cells into more mature, nonreplicating, monocyte-like cells.

Full Text

Duke Authors

Cited Authors

  • Nichols, KE; Weinberg, JB

Published Date

  • April 1989

Published In

Volume / Issue

  • 73 / 5

Start / End Page

  • 1298 - 1306

PubMed ID

  • 2467706

Pubmed Central ID

  • 2467706

International Standard Serial Number (ISSN)

  • 0006-4971

Language

  • eng

Conference Location

  • United States