Induction of erythroid differentiation by the anthracycline antitumor antibiotic pyrromycin.
The oligosaccharide-anthracyclines, aclacinomycin A, marcellomycin and musettamycin, are potent inducers of erythroid differentiation in hemopoietic cells lines of rodent and human origin. The present studies revealed that pyrromycin, a closely related monosaccharide-anthracycline, induced erythroid differentiation in Friend leukemia cells and in the human leukemia cell line K 562. Pyrromycin, marcellomycin and musettamycin, which possess an identical aglycone structure containing a Cl-hydroxyl group, exhibited relatively low optimal inductive concentrations. In contrast, the optimal inductive concentration of aclacinomycin A, which lacks the Cl-hydroxyl group, was markedly higher, i.e., the differentiation inducing capacity was lower. It should be noted, however, that the yield of differentiated cells following treatment with the monosaccharide-anthracycline pyrromycin was distinctly lower than that after treatment with the oligo-saccharide-anthracyclines, aclacinomycin A, marcellomycin or musettamycin. Thus, our data indicate that the efficacy of anthracyclines to induce erythroid differentiation is related to a) the presence of a Cl-hydroxyl group in the aglycone and b) the presence of an oligosaccharide side chain.
Steinheider
G
G
Department of Toxicology, Hamburg University Medical School, Federal Republic of Germany.
Schaefer
A
A
Westendorf
J
J
Marquardt
H
H
D015250:Aclarubicin / Q000494:pharmacology; D000818:Animals; D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002460:Cell Line; D004317:Doxorubicin / Q000494:pharmacology; D004920:Erythropoiesis / Q000187:drug effects*; D005622:Friend murine leukemia virus; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology; D051379:Mice
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; C021736:pyrromycin; D015250:Aclarubicin; D004317:Doxorubicin