Involvement of spermidine in proliferation and differentiation of human
promyelocytic leukemia cells
M Sugiura, T Shafman, T Mitchell, J Griffin and D Kufe
The polyamines putrescine, spermidine, and spermine have been implicated in
the regulation of cell proliferation and differentiation. Previous studies,
however, have demonstrated that the polyamines are essential for
proliferation, but not differentiation, of HL-60 human promyelocytic
leukemia cells. We have extended these findings by demonstrating a highly
significant relationship between intracellular spermidine levels and HL-60
proliferation. However, in contrast to previous studies, we have also
demonstrated that induction of HL-60 differentiation with dimethyl
sulfoxide, hexamethylene bisacetamide, butyric acid, or retinoic acid is
inhibited by alpha-difluoromethyl ornithine (DFMO) depletion of
intracellular putrescine and spermidine. Further, the addition of exogenous
spermidine abrogates DFMO inhibition of HL-60 differentiation, thus
confirming the involvement of this polyamine in the expression of a
differentiated phenotype. The discrepancy between our results and those of
previous studies probably stems from the nearly complete, rather than
partial, depletion of intracellular spermidine achieved in the present
work. The results of the present study thus demonstrate the involvement of
spermidine in both proliferation and induction of HL-60 differentiation
with certain agents.
Volume 63,
Issue 5,
pp. 1153-1158,
05/01/1984
Copyright © 1984 by The American Society of Hematology
