Structure-activity relationship between anthracycline-induced differentiation and inhibition of glycoprotein synthesis in Friend erythroleukemia cells.
The effect of adriamycin, daunomycin, N,N-dimethyladriamycin, N,N-dimethyldaunomycin, pyrromycin, marcellomycin, and aclacinomycin A on erythroid differentiation and glycoprotein synthesis in Friend erythroleukemia cells, clone F4-6 was investigated. Whereas N-dimethylated natural anthracyclines, pyrromycin, marcellomycin, and aclacinomycin A stimulated erythroid differentiation (induction of hemoglobin synthesis), this was not seen with adriamycin, daunomycin and their N-dimethylated derivatives. The incorporation of 3H-mannose in glycoprotein was inhibited by the N-alkylated natural anthracyclines at a concentration at which they induced erythroid differentiation. N,N-Dimethyladriamycin and N,N-dimethyldaunomycin only inhibited 3H-mannose incorporation into glycoprotein at cytotoxic concentrations. However, adriamycin and daunomycin did not inhibit glycoprotein synthesis, even at high cytotoxic concentrations. Aclacinomycin A decreased the incorporation of 3H-mannose into proteins earlier than the incorporation into dolichol-linked oligosaccharide intermediates. Tunicamycin, a specific inhibitor of glycoprotein synthesis, failed to stimulate differentiation in Friend erythroleukemia cells. These results indicate a structure-specific induction of the differentiation and inhibition of glycoprotein synthesis in Friend cells by N-alkylated anthracyclines. The inhibition of glycoprotein synthesis may be involved in the induction of differentiation by N-alkylated anthracyclines, but it cannot be the only target for the differentiation-inducing effect of these substances.
Schaefer
A
A
Department of Toxicology, University of Hamburg Medical School, Germany.
Dahle
M
M
Radenz
G
G
Steinheider
G
G
Marquardt
H
H
D015250:Aclarubicin / Q000494:pharmacology; D000818:Animals; D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003630:Daunorubicin / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000494:pharmacology; D005622:Friend murine leukemia virus; D006023:Glycoproteins / Q000096:biosynthesis*; D006454:Hemoglobins / Q000096:biosynthesis; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism* / Q000473:pathology; D008358:Mannose / Q000378:metabolism; D051379:Mice; D014415:Tunicamycin / Q000494:pharmacology
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D006023:Glycoproteins; D006454:Hemoglobins; D014415:Tunicamycin; C015338:marcellomycin; C021736:pyrromycin; C024886:N,N-dimethyldaunorubicin; C024887:N,N-dimethyldoxorubicin; D015250:Aclarubicin; D004317:Doxorubicin; D008358:Mannose; D003630:Daunorubicin