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.
Mizutani
Y
Y
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan.
Masuoka
S
S
Imoto
M
M
Kawada
M
M
Umezawa
K
K
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