Cisplatin-induced cytotoxicity is blocked by brain-derived neurotrophic factor activation of TrkB signal transduction path in neuroblastoma.
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.
Jaboin
Jerry
J
Cell and Molecular Biology Section, Pediatric Oncology Branch, Center for Cancer Research, NCI, 10 Center Dr. MSC-1928, Bethesda, MD, USA.
Hong
Audrey
A
Kim
Chong Jai
CJ
Thiele
Carol J
CJ
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
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