Possible changes in the intracellular concentrations of
amino acids and
polyamines were investigated during the apoptosis of human promyelocytic leukemic HL-60 cells. Treatment of HL-60 cells with
sodium 5,6-benzylidene-L-ascorbate (SBA) or
sodium ascorbate induced apoptotic cell death characterized by
chromatin condensation, nuclear fragmentation, loss of microvilli, and production of numerous vacuoles and apoptotic bodies. The apoptosis was accompanied by a significant increase in the intracellular concentration of almost all neutral and
basic amino acids (regardless of their polarity). On the other hand, the concentration of
glutamic acid, the most abundant
amino acid in the cells, was significantly reduced. These data suggest the reduced
amino acid utilization and possible membrane impairment, especially in SBA-treated cells. Among three major
polyamines, the intracellular concentration of
putrescine rapidly declined, whereas that of
spermidine and
spermine was almost unchanged during apoptosis. Conversely, the concentration of
putrescine, but not that of
spermidine and
spermine, was significantly increased during the chemically-induced
carcinogenesis of mouse liver tissue. The present study demonstrates that the
putrescine level is the most sensitive to the proliferation capability of the cells, among three
polyamines, and provides an early marker for apoptosis and proliferation.