Induction of erythroid differentiation in leukaemic K562 cells by an S-adenosylhomocysteine hydrolase inhibitor, aristeromycin.
We have isolated an unusual nucleoside, aristeromycin, from the culture filtrate of Actinomycetes as a compound that induces normal morphology in v-ablts-NIH3T3 cells. Aristeromycin also induced erythroid differentiation in abl-expressing human chronic myelogenous leukaemia K562 cells. It did not affect the amount of Abl or the Abl-associated tyrosine kinase activity in either v-ablts-NIH3T3 or K562 cells. As a potent inhibitor of S-adenosylhomocysteine hydrolase, aristeromycin inhibited methylation of phosphatidylethanolamine to form phosphatidylcholine in K562 cells. Among aristeromycin analogues, the activity to inhibit S-adenosylhomocysteine hydrolase was paralleled with the induction of erythroid differentiation. Thus, aristeromycin inhibits abl functions indirectly, possibly by inhibiting biological methylations.
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan.
Y
Y
Mizutani
S
S
Masuoka
M
M
Imoto
M
M
Kawada
K
K
Umezawa
D016475:3T3 Cells; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D043383:Adenosylhomocysteinase; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D004305:Dose-Response Relationship, Drug; D005573:Formycins / Q000494:pharmacology; D016313:Genes, abl; D006801:Humans; D006867:Hydrolases / Q000037:antagonists & inhibitors*; D007536:Isomerism; D007700:Kinetics; D004915:Leukemia, Erythroblastic, Acute; D051379:Mice; D014372:Tubercidin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D005573:Formycins; C018258:3-deazaadenosine; C030034:aristeromycin; C034550:formycin; D006867:Hydrolases; D043383:Adenosylhomocysteinase; D000241:Adenosine; D014372:Tubercidin