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Insulin‐like growth factor I is the key growth factor in serum that protects neuroblastoma cells from hyperosmotic‐induced apoptosis
Author(s) -
Van Golen Cynthia M.,
Feldman Eva L.
Publication year - 2000
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(200001)182:1<24::aid-jcp3>3.0.co;2-6
Subject(s) - apoptosis , neuroblastoma , growth factor , nerve growth factor , biology , microbiology and biotechnology , programmed cell death , insulin like growth factor , endocrinology , medicine , cell culture , biochemistry , receptor , genetics
Neuroblastoma is a childhood tumor of the peripheral nervous system that remains largely uncurable by conventional methods. Mannitol induces apoptosis in neuroblastoma cell types and insulin‐like growth factor I (IGF‐I) protects these cells from hyperosmotic‐induced apoptosis by affecting apoptosis‐regulatory proteins. In the current study, we investigate factors that enable SH‐SY5Y neuroblastoma cells to survive in the presence of an apoptotic stimulus. When SH‐SY5Y cells are exposed to high mannitol concentrations, more than 60% of the cells are apoptotic within 48 h. Normal CS prevents hyperosmotic‐induced apoptosis in a dose‐dependent manner, with 0.6% CS protecting 50% of the cells, and 3% CS rescuing more than 70% of the cells from apoptosis. Serum also delays the commitment point for SH‐SY5Y cells from 9 h to 35 h. A survey of several growth factors, including epidermal growth factor (EGF), platelet‐derived growth factor (PDGF), nerve growth factor (NGF), fibroblast growth factor (FGF), and IGF‐I reveals that IGF‐I is a component of serum necessary for protection of neuroblastoma cells from death. Mitochondrial membrane depolarization occurs in greater than 40% of the cells after mannitol exposure and caspase‐3 activation is increased in high mannitol conditions after 9 h. IGF‐I blocks both the mitochondrial membrane depolarization and caspase‐3 activation normally induced by hyperosmotic treatment in neuroblastoma cells. Our results suggest that (1) IGF‐I is a key factor in serum necessary for protection from death and (2) IGF‐I acts upstream from the mitochondria and the caspases to prevent apoptosis in human neuroblastoma. J. Cell. Physiol. 182:24–32, 2000. © 2000 Wiley‐Liss, Inc.