Insulin-like-growth-factor-I (IGF-I) antagonizes apoptosis induced by serum deficiency and doxorubicin in neuronal cell culture.
We evaluated the effect of insulin-like growth factor (IGF)-I on neuronal cell viability and apoptosis induced by exposure to serum-free (SF) medium and to doxorubicin. In primary neuronal culture, IGF-I (0.5-2.0 microg/ml) slightly increased basal cell viability; SF medium tended to decrease viability (20-27%), and addition of IGF-I significantly antagonized this decrease (P< 0.05). In neuroblastoma (NB) SK-N-SH cell culture, IGF-I significantly increased viability (0.05-1.25 microg/ml) (P< 0.005); SF medium decreased it by 75%, and this decrease was prevented by IGF-I (0.5-1. 0 microg/ml) (P< 0.005). Flow cytometry studies showed an increased apoptosis on exposure to SF medium (88.8 vs 10.2%), which was suppressed to 38.3% by addition of IGF-I. Growth hormone (1-10 microU/ml) did not modify basal cell viability in either culture, and SF-induced cell death in NB cells. Doxorubicin (1-100 microM) caused neurotoxicity in primary and NB cultures (66-39% and 39-10% of controls, respectively), and increased apoptosis in NB cells (73. 8 vs 20.1%). IGF-I antagonized these neurotoxic/apoptotic effects (P< 0.05). This study suggests that IGF-I possesses a potent neuroprotective activity which may be involved in the resistance to doxorubicin.
Gil-Ad
I
I
Laboratory of Biological Psychiatry, Felsenstein Medical Research Center, Beilinson Campus Petah-Tiqva, Israel.
Shtaif
B
B
Luria
D
D
Karp
L
L
Fridman
Y
Y
Weizman
A
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000196:embryology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004317:Doxorubicin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005434:Flow Cytometry; D013006:Growth Hormone / Q000494:pharmacology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D009447:Neuroblastoma; D014407:Tumor Cells, Cultured
D016895:Culture Media, Serum-Free; D007334:Insulin-Like Growth Factor I; D004317:Doxorubicin; D013006:Growth Hormone