title: MAP kinase pathways involved in glioblastoma response to erucylphosphocholine.
abstract: Erucylphosphocholine (ErPC) is a promising antineoplastic drug for the treatment of malignant brain tumors. It exerts strong anticancer activity and induces apoptosis even in chemoresistant glioma cells. In the present study, A172 and U373MG glioma cells were treated with ErPC to explore the contribution of MAP kinase family members ERK, JNK and p38 kinase to ErPC-induced cell death. The exposure to ErPC led to activation of JNK and concurrent inhibition of ERK in both cell lines. Using specific MAP kinase inhibitors we confirmed that in U373MG cells ERK was blocked and JNK was activated upon ErPC treatment. Both effects were dependent on caspase activation. In A172 cells, ErPC treatment resulted in an activation of the JNK pathway, whereas the situation with respect to ERK signalling was more complex. We conclude that inhibition of the ERK pathway by ErPC may be related to antiproliferative effects, while activation of the JNK pathway may be responsible for its pro-apoptotic action.
authors.affiliation: Universitäts-Kinderklinik, D-37099 Göttingen, Germany. wkugler@med.uni-goettingen.de
authors.forename: Wilfried
authors.initials: W
authors.lastname: Kugler
authors.forename: Bernhard
authors.initials: B
authors.lastname: Erdlenbruch
authors.forename: Karoline
authors.initials: K
authors.lastname: Otten
authors.forename: Verena
authors.initials: V
authors.lastname: Jendrossek
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Eibl
authors.forename: Max
authors.initials: M
authors.lastname: Lakomek
mesh_terms: D001932:Brain Neoplasms / Q000201:enzymology* / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000494:pharmacology*; D005909:Glioblastoma / Q000201:enzymology* / Q000473:pathology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000494:pharmacology; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D010767:Phosphorylcholine; C075010:erucylphosphocholine; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases