| Autor: | David S. Middlemas, Brenda K. Kihl, Norma M. Moody |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Brain-derived neurotrophic factor
Cisplatin Cancer Research Programmed cell death biology DNA damage Tropomyosin receptor kinase B medicine.disease nervous system Neurology Oncology Cell culture Neuroblastoma Immunology biology.protein medicine Cancer research Neurology (clinical) Neurotrophin medicine.drug |
| Zdroj: | Journal of Neuro-Oncology. 45:27-36 |
| ISSN: | 0167-594X |
| DOI: | 10.1023/a:1006342423175 |
| Popis: | Neurotrophins are required for survival of neurons during development and may act as survival factors to cells undergoing stress. We tested whether brain derived neurotrophic factor (BDNF) protects neuroblastoma (NB) cells from cytotoxic agents using a model NB cell line, NB 1643, which expresses functional tropomyosin related kinase B (TRKB) following treatment with all-trans-retinoic acid. TRKB is the receptor for BDNF. BDNF increases the EC50 values in survival assays for cisplatin, doxorubicin, and topotecan by two to three fold. Thus, BDNF does indeed protect cells drugs that damage DNA. Cisplatin and doxorubicin are used to treat NB. Topotecan is in clinical studies for the treatment of NB. Since these drugs induce DNA damage, we also investigated whether BDNF might afford protection from γ irradiation. BDNF also induces more than a two fold resistance to γ irradiation. Since BDNF protects cells from agents with different mechanisms of damaging DNA and resistance, it seems likely that BDNF may alter a common signaling pathway required for cell death initiation by DNA damaging agents. |
| Databáze: | OpenAIRE |
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