Structure-activity relationship between anthracycline-induced differentiation and inhibition of glycoprotein synthesis in Friend erythroleukemia cells.

Abstract

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.

• Authors: A Schaefer, M Dahle, G Radenz, G Steinheider, H Marquardt
• Journal: Leukemia (Leukemia) Vol. 5 Issue 2 Pg. 95-100 (Feb 1991) ISSN: 0887-6924 [Print] England
• PMID: 2020200 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anthracyclines
• Antibiotics, Antineoplastic
• Glycoproteins
• Hemoglobins
• Tunicamycin
• marcellomycin
• pyrromycin
• N,N-dimethyldaunorubicin
• N,N-dimethyldoxorubicin
• Aclarubicin
• Doxorubicin
• Mannose
• Daunorubicin

Topics

• Aclarubicin (pharmacology)
• Animals
• Anthracyclines
• Antibiotics, Antineoplastic (pharmacology)
• Cell Differentiation (drug effects)
• Cell Line
• Cell Survival (drug effects)
• Daunorubicin (analogs & derivatives, pharmacology)
• Dose-Response Relationship, Drug
• Doxorubicin (analogs & derivatives, pharmacology)
• Friend murine leukemia virus
• Glycoproteins (biosynthesis)
• Hemoglobins (biosynthesis)
• Leukemia, Erythroblastic, Acute (metabolism, pathology)
• Mannose (metabolism)
• Mice
• Tunicamycin (pharmacology)