The Role of Prostaglandins and Other Arachidonic Acid Metabolites in the Differentiation of HL-60

  • T. R. Breitman
Conference paper
Part of the Proceedings in Life Sciences book series (LIFE SCIENCES)

Abstract

Recently, there has been interest in the possibility that “differentiation inducers” may have utility in the treatment of some malignancies. This concept is predicated on the belief that some malignancies are a result of a block in differentiation which if relieved would result in a more differentiated and therefore more benign malignancy. As a concept for therapy this approach holds the further promise that induction of differentiation could not only relieve the tumor burden but also increase the number of functional cells, the absence of which at least for some malignancies, is a major complication. HL-60 has been a useful model system in the search for substances that are active as inducers of differentiation. HL-60 is induced to differentiate to granulocyte-like cells by incubation with retinoic acid (RA), N,N-dimethylformamide, and dimethyl sulfoxide or into monocyte/macrophage-like cells by incubation with l,25-dihydroxyvitamin D3, butyrate, and 12-O-tetradecanoyl phorbol-13-acetate (TPA). Of the many compounds that induce differentiation of HL-60, RA has probably the most promise of being of use in the clinic. This is because it is active at physiological concentrations in vitro; has been shown to induce differentiation of fresh human leukemia cells in primary culture; and has been reported to be effective on patients with some leukemias. To the extent that it is possible, results in vitro should suggest treatments in vivo. To this end we have been interested in determining which induction conditions result in the most “normal” mature HL-60. The studies to be presented indicate that combinations of RA and PGE2 synergistically induce the differentiation of HL-60 and that differentiated HL-60 cells are functional in producing cyclooxygenase and lipoxygenase products from arachidonic acid.

Keywords

DMSO Leukemia Cortisol Aspirin Dexamethasone 

Abbreviations

RA

retinoic acid

PG

prostaglandin

NBT

nitrobluetetrazolium

HMBA

hexamethylene-bis-acetamide

DMSO

dimethylsulfoxide

DMF

dimethylformamide

NDGA

nordihydroguaiaretic acid.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Berenbaum MC, Cope WA, Bundick RV (1976) Synergistic effect of Cortisol and prostaglandin E2 on the PHA response. Clin Exp Immuno 26: 535–541Google Scholar
  2. Breitman TR, Keene BR (1982) Growth and differentiation of human promyelocytic cell line HL-60 in a defined medium. Cold Spring Harbor Conf Cell Proliferation 9: 691–702Google Scholar
  3. Breitman TR, Keene BR, Hemmi H (1983) Retinoic acid-induced differentiation of fresh human leukaemia cells and the human myelomonocytic leukaemia cell lines, HL-60, U-937, and THP-1. Cancer Surveys 2: 263–291Google Scholar
  4. Breitman TR, Keene BR, Hemmi H (1984) Studies of growth and differentiation of human myelomonocytic leukemia cell lines in serum-free medium. In: Barnes DW, Sirbasku DA, Sato GH (eds) Methods for Serum-Free Culture of Neuronal and Lymphoid Cells. Alan R Liss, New York, pp 215–236Google Scholar
  5. Imaizumi M, Breitman TR (1986) A combination of a T cell-derived lymphokine differentiation-inducing activity and a physiologic concentration of retinoic acid induces HL-60 to differentiate to cells with functional chemotactic peptide receptors. Blood 67: 1273–1280PubMedGoogle Scholar
  6. Jaffe BM, Behrman HR, Parker CW (1973) Radioimmunoassay measurement of prostaglandin E, A, and F in human plasma. J Clin Invest 52: 398–405Google Scholar
  7. Levine L, Ohuchi K (1978) Retinoids as well as tumour promoters enhance deacylation of cellular lipids and prostaglandin production in MDCK cells. Nature 276: 274–275PubMedCrossRefGoogle Scholar
  8. Levine L, Morgan RA, Lewis RA, Austen KF, Clark DA, Marfat A, Corey EJ (1981) Radioimmunoassay of the leukotrienes of slow reacting substance of anaphylaxis. Proc Natl Acad Sci USA 78: 7692–7696PubMedCrossRefGoogle Scholar
  9. McCarthy DM, San Miguel JF, Freake HC, Green PM, Zola H, Catovsky D, Goldman JM (1983) 1,25-Dihydroxyvitamin D3 inhibits proliferation of human promyelocytic leukemia (HL-60) cells and induces monocyte-macrophage differentiation in HL-60 and normal human bone marrow cells. Leuk Res 7: 51–55Google Scholar
  10. Miyaura C, Abe E, Kuribayashi T, Tanaka H, Konno K, Nishii Y, SudaT (1981) 1,25-Dihydroxyvitamin D3 induces differentiation of human myeloid leukemia cells. Biochem Biophys Res Commun 102: 937–943Google Scholar
  11. Napoli JL, Pramanik BC, Williams JB, Dawson MI, Hobbs PD (1985) Quantification of retinoic acid by gas-liquid chromatography-mass spectrometry: total versus all-trans-retinoic acid in human plasma. J Lipid Res 26: 387–392PubMedGoogle Scholar
  12. Olsson IL, Breitman TR, Gallo RC (1982) Priming of human myeloid leukemic cell lines HL-60 and U-937 with retinoic acid for differentiation effects of cyclic adenosine 3′:5′-monophos- phate-indueing agents and a T-lymphocyte-derived differentiation factor. Cancer Res 42: 3928–3933PubMedGoogle Scholar
  13. Shiina Y, Abe E, Miyaura C, Tanaka H, Yamada S, Ohmori M, Nakayama K, Takayama H, Matsunaga I, Nishii Y, Deluca HF, Suda T (1983) Biological activity of 24,24-difluoro-l,25-dihy- droxyvitamin D3 26,23-lactone in inducing differentiation of human myeloid leukemia cells. Arch Biochem Biophys 220: 90–94PubMedCrossRefGoogle Scholar
  14. Skubitz KM, Zhen Y, August JT (1982) Dexamethasone synergistically induces chemotactic peptide receptor expression in HL-60 cells. Blood 59: 586–593PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1987

Authors and Affiliations

  • T. R. Breitman
    • 1
  1. 1.Laboratory of Biological Chemistry, Developmental Therapeutics Program, Division of Cancer TreatmentNational Cancer InstituteBethesdaUSA

Personalised recommendations