Induction of the differentiation of HL-60 and WEHI-3B D+ leukemia cells by lithium chloride.
The use of lithium chloride in manic-depressive patients and in patients receiving myelo-suppressive cancer chemotherapeutic agents is accompanied by a sustained leukocytosis due to an increase in granulocyte production. This property suggests that lithium chloride may have effects on hematopoietic differentiation. Treatment of cultured WEHI-3B D+ murine myelomonocytic and HL-60 human promyelocytic leukemia cells with millimolar concentrations of lithium chloride resulted in concentration-dependent increases in the number of differentiated myeloid cells, as determined by the ability of the cells to reduce nitroblue tetrazolium and by the binding of myeloid specific antibodies, and was associated with an inhibition of cellular proliferation. The effects of lithium chloride on growth and differentiation were antagonized by KCl, whereas NaCl had little effect. The induction of leukemic cell maturation by lithium chloride was markedly enhanced by the addition of low levels of retinoic acid. In contrast, other differentiation inducing agents (i.e. dimethyl sulfoxide and selenazofurin) had no effect on the degree of maturation induced by lithium. These findings suggest that the combination of lithium chloride and retinoic acid may have clinical utility in the treatment of leukemia through the induction of terminal differentiation.
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510.
J A
JA
Sokoloski
J
J
Li
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A
Nigam
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AC
Sartorelli
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002712:Chlorides / Q000494:pharmacology*; D006133:Growth Substances / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D015479:Leukemia, Myelomonocytic, Acute / Q000188:drug therapy / Q000473:pathology*; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000473:pathology*; D008094:Lithium / Q000494:pharmacology*; D018021:Lithium Chloride; D051379:Mice; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D002712:Chlorides; D006133:Growth Substances; D014212:Tretinoin; D008094:Lithium; D018021:Lithium Chloride