Apoptotic cell death induced by serum and its prevention by thiols

We recently reported that serum contains low molecular weight factors that inhibit growth and cause cell death in vitro. The present study focused on identifying components of basal media that counteract the toxic effects of serum. Amino acids L-cyst(e)ine and L-tryptophan were found to prevent serum-induced cell death of TIG-1 human fetal lung fibroblasts and other cell types. In addition to L-cysteine, other thiol-bearing and dithiol-cleaving compounds showed a similar ability to rescue the cells. Various inhibitors of protein or RNA synthesis also prevented the cell death. By contrast, nonthiol-containing reducing agents and super oxide dismutase (SOD), an active oxygen-eliminating enzyme, were ineffective. Thiol compounds appeared to exert a supportive level in TIG-1 cells cultured in FBS, whereas protein synthesis inhibitors did not alter the reduced intracellular thiol content. Fragmentation of DNA occurred prior to the plasma membrane breakdown of dying cells. Taken together, these data suggest that serum-induced cell death represents a form of apoptosis in which molecules containing thiol groups are active participants.