New insight into oncoprotein-targeted antitumor effect: herbimycin A as an antagonist of protein tyrosine kinase against Ph1-positive leukemia cells.
Herbimycin A, a benzoquinonoid anasamycin antibiotic, has been shown to reserve the oncogenic phenotypes of p60v-src transformed cells by the virtue of the inhibition of src protein tyrosine kinase. Furthermore, we previously demonstrated that herbimycin A displayed the antitumor activity on Ph1-positive leukemia cells and bcr/abl oncoprotein-associated transformed murine hematopoietic cells with the transfection of a retroviral vector expressing bcr/abl. Herbimycin A showed preferential inhibition on the in vitro growth of Ph1-positive leukemia cells and bcr/abl oncoprotein-associated murine hematopoietic cells through the inhibition of bcr/abl tyrosine kinase activity and the reduction of subsequent phosphotyrosyl proteins. Recently, from the view of investigating the oncogenic significance or of developing a future clinical application in malignancies, several developing agents targeted against oncoprotein have been tried. We reviewed the present progress in the mechanism of oncoprotein-targeted antitumor effects and focused on herbimycin A-induced antitumor activity on Ph1-positive leukemia cells.
Okabe
M
M
Third Department of Internal Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Uehara
M
M
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D016227:Benzoquinones; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D016044:Fusion Proteins, bcr-abl / Q000096:biosynthesis*; D006801:Humans; D047029:Lactams, Macrocyclic; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000633:toxicity; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000633:toxicity; D011809:Quinones / Q000627:therapeutic use* / Q000633:toxicity; D017828:Rifabutin / Q000031:analogs & derivatives; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D016227:Benzoquinones; D047029:Lactams, Macrocyclic; D016376:Oligonucleotides, Antisense; D011809:Quinones; D017828:Rifabutin; C020754:herbimycin; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl