Induction of leukemia cell differentiation by chemotherapeutic agents

Edward L. Schwartz, Kimiko Ishiguro, Alan C. Sartorelli

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The antineoplastic agents marcellomycin (and related anthracycline antibiotics) and 6-thioguanine are effective induces of the differentiation of cultured leukemia cells. Studies designed to investigate the relationship between structure and activity conducted with the anthracyclines in HL-60 human acute promyeloctic leukemia cells indicated a dissociation between cytotoxicity and maturation-inducing properties of these agents. In an analogous manner, 6-thioguanine induced effective erythroid and granulocytic differentiaion of Friend and HL-60 leukemias, respectively, only in hypoxanthine-guanine phosphoribosyltransferase deficient cells. These findinds suggest that 6-thioguanine need not be metabolized to a nucleotide to be active as an inducer of differentiation, and that the concentration is greater than that producing cytotoxicity. Erythrodifferntiation of HGPRT negative Friend murine leukemia cells by 6-thioguanine was antagonized by tetracaine, d,1-propanolol and 12-O-tetradecanoylphorbol-13-acetate, providing evidence for acell membrand mediated component in the action of the purine antimetabolite. This suggests that the biochemical events that produce differentiation after exposure to 6-thioguanine may differ from those responsible for the toxic actions of the drug. Studies such as these, designed to gain an understanding of he target sites of inducers of differentiation, may lead to the development of new agents of potential therapeutic benefit in the treatment of certain forms of cancer based on the conversion of malignant cells to their non-proliferating mature counterparts.

Original languageEnglish (US)
Pages (from-to)3-20
Number of pages18
JournalAdvances in Enzyme Regulation
Volume21
Issue numberC
DOIs
StatePublished - 1983
Externally publishedYes

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Thioguanine
Cell Differentiation
Leukemia
Hypoxanthine Phosphoribosyltransferase
Anthracyclines
Cytotoxicity
Tetracaine
Toxic Actions
Antimetabolites
Tetradecanoylphorbol Acetate
Structure-Activity Relationship
Propranolol
Antineoplastic Agents
Cultured Cells
Acetates
Nucleotides
Anti-Bacterial Agents
Therapeutics
Pharmaceutical Preparations
Neoplasms

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Induction of leukemia cell differentiation by chemotherapeutic agents. / Schwartz, Edward L.; Ishiguro, Kimiko; Sartorelli, Alan C.

In: Advances in Enzyme Regulation, Vol. 21, No. C, 1983, p. 3-20.

Research output: Contribution to journalArticle

Schwartz, Edward L. ; Ishiguro, Kimiko ; Sartorelli, Alan C. / Induction of leukemia cell differentiation by chemotherapeutic agents. In: Advances in Enzyme Regulation. 1983 ; Vol. 21, No. C. pp. 3-20.
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