ONO-4007, a new synthetic lipid A derivative, induces differentiation of rat myelomonocytic leukemia cells in vitro and in vivo.
We have examined the differentiation-inducing effects of ONO-4007, a new synthetic lipid A derivative with low endotoxic activities, on a rat myelomonocytic cell line, c-WRT-7, in vitro and in vivo. ONO-4007 induced the differentiation of c-WRT-7 cells into macrophage-like cells and inhibited the proliferation of c-WRT-7 cells in vitro. Stimulation with ONO-4007 induced messenger RNA expression of interleukin-1 alpha (IL-1 alpha), IL-6, and tumor necrosis factor-alpha (TNF-alpha), which have been reported to induce differentiation of several leukemia cell lines. However, autocrine production of these cytokines may not be involved in the mechanisms of differentiation induced by ONO-4007, because the treatment with IL-1 alpha, IL-6, or TNF-alpha does not induce the differentiation of c-WRT-7 cells. In vivo treatment by intravenous administration of ONO-4007 resulted in a significant prolongation of survival time of the rats inoculated intravenously with c-WRT-7 cells compared with that of untreated rats. These results suggest that ONO-4007 can be therapeutically useful for the treatment of leukemia.
Kobayashi
M
M
Laboratory of Pathology, Hokkaido University School of Medicine, Sapporo, Japan.
Nagayasu
H
H
Hamada
J
J
Takeichi
N
N
Hosokawa
M
M
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D016227:Benzoquinones; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D007951:Leukemia, Myeloid / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D008050:Lipid A / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D008969:Molecular Sequence Data; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011809:Quinones / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D017828:Rifabutin / Q000031:analogs & derivatives; D019311:Staurosporine; D013449:Sulfonamides / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology
D000470:Alkaloids; D016227:Benzoquinones; D002147:Calmodulin; D007375:Interleukin-1; D015850:Interleukin-6; D047029:Lactams, Macrocyclic; D008050:Lipid A; C086889:ONO 4007; D011809:Quinones; D012333:RNA, Messenger; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D017828:Rifabutin; C017967:W 7; C020754:herbimycin; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D019311:Staurosporine