PMID: 6400065Jan 1, 1983Paper

Induction of leukemia cell differentiation by chemotherapeutic agents

Advances in Enzyme Regulation
E L SchwartzA C Sartorelli

Abstract

The antineoplastic agents marcellomycin (and related anthracycline antibiotics) and 6-thioguanine are effective inducers 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 promyelocytic 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 differentiation of Friend and HL-60 leukemias, respectively, only in hypoxanthine-guanine phosphoribosyltransferase deficient cells. These findings suggest that 6-thioguanine need not be metabolized to a nucleotide to be active as an inducer of differentiation, and that the concentration of the 6-thiopurine required to initiate the commitment to maturation is greater than that producing cytotoxicity. Erythrodifferentiation of HGPRT negative Friend murine leukemia cells by 6-thioguanine was antagonized by tetracaine, d, 1-propranolol and 12-O-tetradecanoylphorbol-13-acetate, providing evidence for a cell membrane mediated component in the action of the purine antimetabolite. This suggests that the biochemical events that ...Continue Reading

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Citations

Jan 1, 1990·The International Journal of Biochemistry·K PavelićS Spaventi
Jan 1, 1986·Advances in Enzyme Regulation·A C SartorelliM Reiss
Dec 4, 2003·Pharmacology & Therapeutics·Asterios S TsiftsoglouIoannis S Vizirianakis
Mar 1, 1991·The Journal of Investigative Dermatology·M J EdwardsM R O'Donovan
May 15, 2020·Medicinal Chemistry·Hina SiddiquiSyed Ghulam Musharraf

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