PMID- 10728907
OWN - NLM
STAT- MEDLINE
DCOM- 20000411
LR  - 20211116
IS  - 0167-594X (Print)
IS  - 0167-594X (Linking)
VI  - 45
IP  - 1
DP  - 1999
TI  - Brain derived neurotrophic factor protects human neuroblastoma cells from DNA 
      damaging agents.
PG  - 27-36
AB  - 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 gamma irradiation. BDNF also induces more than a two fold 
      resistance to gamma 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.
FAU - Middlemas, D S
AU  - Middlemas DS
AD  - Department of Molecular Pharmacology, St. Jude Children's Research Hospital, 
      Memphis, TN 38105, USA. david.middlemas@stjude.org
FAU - Kihl, B K
AU  - Kihl BK
FAU - Moody, N M
AU  - Moody NM
LA  - eng
GR  - 1 R29 CA 71628/CA/NCI NIH HHS/United States
GR  - CA 21765/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurooncol
JT  - Journal of neuro-oncology
JID - 8309335
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (DNA, Neoplasm)
RN  - 0 (Neuroprotective Agents)
RN  - 7M7YKX2N15 (Topotecan)
RN  - 80168379AG (Doxorubicin)
RN  - Q20Q21Q62J (Cisplatin)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Cisplatin/pharmacology
MH  - DNA Damage/drug effects
MH  - DNA, Neoplasm/drug effects/radiation effects
MH  - Doxorubicin/pharmacology
MH  - Gamma Rays
MH  - Humans
MH  - Neuroblastoma/*genetics/pathology
MH  - Neuroprotective Agents/*pharmacology
MH  - Topotecan/pharmacology
MH  - Tumor Cells, Cultured/drug effects/radiation effects
EDAT- 2000/03/23 09:00
MHDA- 2000/04/15 09:00
CRDT- 2000/03/23 09:00
PHST- 2000/03/23 09:00 [pubmed]
PHST- 2000/04/15 09:00 [medline]
PHST- 2000/03/23 09:00 [entrez]
AID - 10.1023/a:1006342423175 [doi]
PST - ppublish
SO  - J Neurooncol. 1999;45(1):27-36. doi: 10.1023/a:1006342423175.