title: Oleic acid is the active component in the mushroom Daedalea gibbosa inhibiting Bcr-Abl kinase autophosphorylation activity.
abstract: The hallmark of chronic myeloid leukemia (CML) is the abnormal activity of p210(Bcr-Abl) kinase. Selective kinase inhibitors such as imatinib or nilotinib have been established successfully for the treatment of CML. Despite high rates of clinical response, CML patients can develop resistance to these kinase inhibitors mainly due to point mutations within the Abl kinase domain of the fusion protein. Previously, we reported that a crude extract of the mushroom Daedalea gibbosa inhibited kinase activity of Bcr-Abl kinase. Here we report on the identification of the active component of Daedalea gibbosa, oleic acid, which inhibited Bcr-Abl kinase autophosphorylation in Ba/F3 cells and exhibited anti-CML activity in a BCR/ABL-positive mouse model.
authors.affiliation: Cancer Drug Discovery Program, Migal, Kiryat Shmona, 11016, Israel. jamalm@migal.org.il
authors.forename: Hazem
authors.initials: H
authors.lastname: Khamaisie
authors.forename: Sherbel
authors.initials: S
authors.lastname: Sussan
authors.forename: Michael
authors.initials: M
authors.lastname: Tal
authors.forename: Yousef
authors.initials: Y
authors.lastname: Najajreh
authors.forename: Martin
authors.initials: M
authors.lastname: Ruthardt
authors.forename: Jamal
authors.initials: J
authors.lastname: Mahajna
mesh_terms: D000363:Agaricales / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000201:enzymology; D051379:Mice; D008819:Mice, Nude; D019301:Oleic Acid / Q000302:isolation & purification / Q000627:therapeutic use*; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000627:therapeutic use*; D054448:Precursor Cells, B-Lymphoid / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D010936:Plant Extracts; D047428:Protein Kinase Inhibitors; D019301:Oleic Acid; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl