Dimethyl sulfoxide inhibits the binding of granulocyte/macrophage colony-stimulating factor and insulin to their receptors on human leukemia cells.
Numerous agents can induce the terminal differentiation of leukemia cells in vitro, and this action has been found to be of therapeutic value in the treatment of acute promyelocytic leukemia. The proximal site of action of the prototypical chemical inducer of differentiation, dimethyl sulfoxide (DMSO), is not known. In this study, DMSO was found to rapidly cause a 45% to 85% reduction in the specific binding of the growth factors granulocyte/macrophage colony-stimulating factor and insulin to their respective cell surface receptors on HL-60 human acute promyelocytic leukemia cells. Significant inhibition of binding was first observed after 30 min of DMSO treatment, occurred at both 4 degrees C and 37 degrees C, and was due to a DMSO-induced decrease in apparent receptor affinity, with little change in receptor number. A similar inhibition of insulin binding was seen with a second inducer of differentiation, hexamethylene bisacetamide. Kinetic studies demonstrated that DMSO enhanced the rate of insulin dissociation from its receptor. The inhibition of insulin binding by DMSO was also observed in a cell-free extract, suggesting that the effect was not a cell-mediated response to DMSO treatment. DMSO blocked the insulin-induced stimulation of protein tyrosine phosphorylation. These studies suggest that one action of DMSO may be the disruption of the structure and/or organization of cell surface receptors that regulate growth and differentiation.
Schwartz
E L
EL
Department of Oncology, Albert Einstein College of Medicine, Bronx, New York 10467.
Chamberlin
H
H
Ravichander
P
P
Whitbread
J A
JA
D002454:Cell Differentiation / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism; D011972:Receptor, Insulin / Q000187:drug effects* / Q000378:metabolism; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000187:drug effects* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D007328:Insulin; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011972:Receptor, Insulin; D004121:Dimethyl Sulfoxide