TRANSIENT INDUCTION OF APOPTOSIS IN SERUM-STARVED GLIOMA-CELLS BY INSULIN AND IGF-1

Insulin has a wide variety of biological effects, One of them is a mit ogen-like activity whereby cell proliferation is stimulated. In this s tudy we found a heretofore unreported insulin-elicited transient apopt osis of glioma cells. When serum-starved glioma cells were fed with a fresh regular medium, in the 6- to 12-h post-starvation period, the gr owth rate as determined by cell number was significantly suppressed by insulin, although cell cycle progression and DNA synthesis were actua lly accelerated. Increase in apoptosis in those growth-retarded cultur es was demonstrable by Hoechst staining, detection of histone-associat ed DNA fragment, and in situ cell death detection. Apoptosis occurred among cells in all stages of cell cycle. After 24 h post-starvation, i nsulin increased the total cell number like a typical growth-promoting mitogen. In this regard, IGF-1, but not EGF nor TGF-beta 1, behaved l ike insulin.