title: Cisplatin-induced cytotoxicity is blocked by brain-derived neurotrophic factor activation of TrkB signal transduction path in neuroblastoma.
abstract: We evaluated the ability of brain-derived neurotrophic factor (BDNF) to decrease the chemosensitivity of neuroblastoma cells to cisplatin. Two cell lines, one derived from SH-SY5Y (SY5Y-TB8) and the other from SK-N-AS (AS-TB8), transfected with a TrkB plasmid were generated, and used to assess the effects of activation of the TrkB signal transduction path on cisplatin (Cis) induced apoptosis. BDNF treatment of each of the TrkB expressing cells blocked cisplatin-induced cell death. BDNF's ability to rescue the cells from cisplatin-induced cell death was inhibited by treatment with the Trk tyrosine kinase inhibitor, K252a, and the phosphatidylinositol 3'-kinase (PI)-3-kinase inhibitor, LY294002. This indicates that the activation of the TrkB path through PI-3-kinase is required for BDNF's survival-promoting effects.
authors.affiliation: Cell and Molecular Biology Section, Pediatric Oncology Branch, Center for Cancer Research, NCI, 10 Center Dr. MSC-1928, Bethesda, MD, USA.
authors.forename: Jerry
authors.initials: J
authors.lastname: Jaboin
authors.forename: Audrey
authors.initials: A
authors.lastname: Hong
authors.forename: Chong Jai
authors.initials: CJ
authors.lastname: Kim
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Thiele
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002867:Chromones / Q000494:pharmacology; D002945:Cisplatin / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D009025:Morpholines / Q000494:pharmacology; D009447:Neuroblastoma / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011233:Precipitin Tests; D020813:Receptor, trkB / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D019208:Brain-Derived Neurotrophic Factor; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D011994:Recombinant Proteins; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases; D020813:Receptor, trkB; D002945:Cisplatin