Insulin-like-growth-factor-I (IGF-I) antagonises apoptosis induced by serum deficiency and doxorubicin in neuronal cell culture

We evaluated the effect of insulin-like growth factor (IGF)-I on neuronal c ell viability and apoptosis induced by exposure to serum-free (SF) medium a nd to doxorubicin. In primary neuronal culture, IGF-I (0.5-2.0 mu g/ml) sli ghtly increased basal cell viability; SF medium tended to decrease viabilit y (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 mu g/ml) (P < 0.005); SF medium decreased it by 75%, and this decrease was prevented by IGF-I (0.5-1.0 mu g/ml) (P < 0. 005). Flow cytometry studies showed an increased apoptosis on exposure to S F medium (88.8 vs 10.2%), which was suppressed to 38.3% by addition of IGF- I. Growth hormone (1-10 mu U/ml) did not modify basal cell viability in eit her culture, and SF-induced cell death in NE cells. Doxorubicin (1-100 mu M ) caused neurotoxicity in primary and NE cultures (66-39% and 39-10% of con trols, respectively), and increased apoptosis in NE 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. (C) 1999 Harcourt Publishers Ltd.