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Nordihydroguaiaretic acid inhibits insulin-like growth factor signaling, growth, and survival in human neuroblastoma cells
Journal of cellular biochemistry, 2007-12, Vol.102 (6), p.1529-1541
Meyer, Gary E.
Chesler, Louis
Liu, Dandan
Gable, Karissa
Maddux, Betty A.
Goldenberg, David D.
Youngren, Jack F.
Goldfine, Ira D.
Weiss, William A.
Matthay, Katherine K.
Rosenthal, Stephen M.
2007
Volltextzugriff (PDF)
Details
Autor(en) / Beteiligte
Meyer, Gary E.
Chesler, Louis
Liu, Dandan
Gable, Karissa
Maddux, Betty A.
Goldenberg, David D.
Youngren, Jack F.
Goldfine, Ira D.
Weiss, William A.
Matthay, Katherine K.
Rosenthal, Stephen M.
Titel
Nordihydroguaiaretic acid inhibits insulin-like growth factor signaling, growth, and survival in human neuroblastoma cells
Ist Teil von
Journal of cellular biochemistry, 2007-12, Vol.102 (6), p.1529-1541
Ort / Verlag
Hoboken: Wiley Subscription Services, Inc., A Wiley Company
Erscheinungsjahr
2007
Quelle
MEDLINE
Beschreibungen/Notizen
Neuroblastoma is a common pediatric malignancy that metastasizes to the liver, bone, and other organs. Children with metastatic disease have a less than 50% chance of survival with current treatments. Insulin‐like growth factors (IGFs) stimulate neuroblastoma growth, survival, and motility, and are expressed by neuroblastoma cells and the tissues they invade. Thus, therapies that disrupt the effects of IGFs on neuroblastoma tumorigenesis may slow disease progression. We show that NVP‐AEW541, a specific inhibitor of the IGF‐I receptor (IGF‐IR), potently inhibits neuroblastoma growth in vitro. Nordihydroguaiaretic acid (NDGA), a phenolic compound isolated from the creosote bush (Larrea divaricata), has anti‐tumor properties against a number of malignancies, has been shown to inhibit the phosphorylation and activation of the IGF‐IR in breast cancer cells, and is currently in Phase I trials for prostate cancer. In the present study in neuroblastoma, NDGA inhibits IGF‐I‐mediated activation of the IGF‐IR and disrupts activation of ERK and Akt signaling pathways induced by IGF‐I. NDGA inhibits growth of neuroblastoma cells and induces apoptosis at higher doses, causing IGF‐I‐resistant activation of caspase‐3 and a large increase in the fraction of sub‐G0 cells. In addition, NDGA inhibits the growth of xenografted human neuroblastoma tumors in nude mice. These results indicate that NDGA may be useful in the treatment of neuroblastoma and may function in part via disruption of IGF‐IR signaling. J. Cell. Biochem. 102: 1529–1541, 2007. © 2007 Wiley‐Liss, Inc.
Sprache
Englisch
Identifikatoren
ISSN: 0730-2312
eISSN: 1097-4644
DOI: 10.1002/jcb.21373
Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3001106
Format
–
Schlagworte
Animals
,
apoptosis
,
Apoptosis - drug effects
,
Caspase 3 - metabolism
,
Cell Culture Techniques
,
Cell Movement - drug effects
,
Cell Proliferation - drug effects
,
Cell Survival - drug effects
,
Cells, Cultured
,
Dose-Response Relationship, Drug
,
Enzyme Activation - drug effects
,
Extracellular Signal-Regulated MAP Kinases - metabolism
,
Humans
,
Insulin-Like Growth Factor I - antagonists & inhibitors
,
insulin-like growth factor I receptor
,
Masoprocol - pharmacology
,
Mice
,
Mice, Nude
,
neuroblastoma
,
Neuroblastoma - drug therapy
,
Neuroblastoma - pathology
,
nordihydroguaiaretic acid
,
Phosphorylation - drug effects
,
Propidium - metabolism
,
Proto-Oncogene Proteins c-akt - antagonists & inhibitors
,
Pyrimidines - pharmacology
,
Pyrroles - pharmacology
,
Receptor, IGF Type 1 - antagonists & inhibitors
,
Signal Transduction - drug effects
,
small molecule inhibitor
,
Xenograft Model Antitumor Assays
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