Inhibition by erythroid differentiation factor (activin A) of P-glycoprotein expression in multidrug-resistant human K562 erythroleukemia cells

The K562/VCR cell line, exhibiting acquired multidrug resistance (MDR) with increased expression of a cell surface glycoprotein (P-glycoprotein), was isolated from human erythroleukemia K562 cells. Various compounds that induced erythroid differentiation of K562 cells were tested for their effects o...

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Published inCancer research (Chicago, Ill.) Vol. 51; no. 10; pp. 2582 - 2586
Main Authors Okabe-Kado, J, Hayashi, M, Honma, Y, Hozumi, M, Tsuruo, T
Format Journal Article
LanguageEnglish
Published United States 15.05.1991
Subjects
activin A
Activins
ATP-Binding Cassette, Sub-Family B, Member 1
Cell Differentiation - drug effects
Cell Line
Cell Survival - drug effects
Doxorubicin - pharmacology
Drug Resistance - genetics
erythroid inhibition factor
erythroleukemia
expression
Humans
Inhibins - pharmacology
inhibition
K-562 cells
Kinetics
Leukemia, Promyelocytic, Acute
man
Membrane Glycoproteins - analysis
Membrane Glycoproteins - biosynthesis
P-glycoprotein
Vincristine - pharmacology
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Summary:The K562/VCR cell line, exhibiting acquired multidrug resistance (MDR) with increased expression of a cell surface glycoprotein (P-glycoprotein), was isolated from human erythroleukemia K562 cells. Various compounds that induced erythroid differentiation of K562 cells were tested for their effects on growth and differentiation of these K562/VCR cells. Sodium butyrate, hemin, 1-beta-D-arabinofuranosylcytosine, and erythroid differentiation factor (EDF) induced erythroid differentiation of K562/VCR cells as well as K562 cells. The MDR of K562/VCR cells was partly overcome by treatment with EDF but not with the other inducers. Expression of P-glycoprotein by K562/VCR cells was measured by radioimmunoassay using MRK16 monoclonal antibody. Results showed that EDF caused down-regulation of P-glycoprotein in K562/VCR cells, whereas the other inducers did not cause its down-regulation. Thus, in addition to inducing erythroid differentiation, EDF enhanced the sensitivity of K562/VCR cells to multidrugs and suppressed expression of P-glycoprotein. These results suggest that differentiation inducers may be useful in chemotherapy of leukemic MDR cells.
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ISSN:0008-5472