Dimethyl sulfoxide inhibits the binding of granulocyte/macrophage colony-stimulating factor and insulin to their receptors on human leukemia cells.
نویسندگان
چکیده
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.
منابع مشابه
Enhanced mitogenic responsiveness to granulocyte-macrophage colony-stimulating factor in HL-60 promyelocytic leukemia cells upon induction of differentiation.
Treatment of HL-60 leukemia cells with the inducers of differentiation dimethyl sulfoxide (DMSO) and 6-thioguanine (TG) reduces the proliferative capacity of the cells. DMSO acted in a serum-independent manner and reversibly inhibited competence to enter S phase after 24 h of treatment. Purified human granulocyte-macrophage colony-stimulating factor (GM-CSF) but not human CSF-1, restored S phas...
متن کاملAdvances in Hematopoietic Stem Cell Mobilization and Peripheral Blood Stem Cell Transplantation
Hematopoietic stem/progenitor cells (HSPCs) which give rise to different blood cell types are present within the bone marrow microenvironment, especially in flat bones such as skull, vertebrae, pelvis and chest. Interacting factors such as stromal derived factor-1/CXCR4, very late antigen-4/vascular cell adhesion molecule-1, Lymphocyte function-associated antigen-1/ intercellular adhesion molec...
متن کاملExpression and Secretion of Human Granulocyte Macrophage-Colony Stimulating Factor Using Escherichia coli Enterotoxin I Signal Sequence
With the aim of the secretion of human granulocyte macrophage-colony stimulating factor (hGM-CSF) in Escherichia coli, hGM-CSF cDNA was fused in-frame next to the signal sequence of ST toxin (ST-I) of exteroxigenic E. coli, containing 53 or 19 amino acids of signal peptide. The fused STsig::hGM-CSF coding fragments were inserted into a T7-based expression plasmid. The recombinant plasmids were ...
متن کاملComparison of T7- and Lac-Based Systems for the Periplasmic Expression of Human Granulocyte Macrophage Colony Stimulating Factor in Escherichia coli
متن کامل
Hck expression correlates with granulocyte-macrophage colony-stimulating factor-induced proliferation in HL-60 cells.
The human myeloid cell line HL-60 expresses approximately 300 high-affinity granulocyte-macrophage colony-stimulating factor receptors (GM-CSFRs), yet treatment of these cells with GM-CSF does not result in enhanced cellular proliferation or increases in protein tyrosine phosphorylation. In contrast, GM-CSF induces rapid increases in protein tyrosine phosphorylation and proliferative responses ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Cancer research
دوره 53 5 شماره
صفحات -
تاریخ انتشار 1993