A New Group of Potent Inducers of Differentiation in Murine Erythroleukemia Cells

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 73; no. 3; pp. 862 - 866
• Main Authors: Reuben, Roberta C., Wife, Richard L., Breslow, Ronald, Rifkind, Richard A., Marks, Paul A.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 01.03.1976; National Acad Sciences
• Subjects: Acetamides - pharmacology; Acute erythroblastic leukemia; Benzidines - metabolism; Cell Differentiation - drug effects; Cell growth; Cell Line; Cell lines; Cells; Cellular differentiation; Cultured cells; Diamines; Dimers; Dimethyl Sulfoxide - pharmacology; Hemoglobins; Hemoglobins - biosynthesis; Leukemia, Erythroblastic, Acute - metabolism; Leukemia, Erythroblastic, Acute - pathology; Mice; Structure-Activity Relationship
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.73.3.862

This report identifies a group of compounds, polymethylene bisacetamides (acetylated diamines), which are potent inducers of erythroid differentiation in murine erythroleukemia cells. A known inducing agent, N-methylacetamide, was dimerized through varying numbers of methylenes in an attempt to increase the local effective concentration at adjacent target sites. The simple dimer was no more effective than N-methylacetamide alone; introduction of five to eight methylenes between acetamide groups substantially increased the effectiveness of these compounds. The hexamethylene bisacetamide was active between 0.5 mM and 5 mM; the percentage of cells induced and the rate at which they were recruited to differentiation was dependent upon the concentration of inducer within this range. At 5 mM hexamethylene bisacetamide essentially the entire population (>99%) was induced to a pathway of erythroid differentiation which was greater differentiation of the cultured cells than with any inducer yet tested.