The effects of
canavalmine, a structural analogue of
spermine, were studied in cultured murine
erythroleukemia cells 745A.
Canavalmine exerted an inhibition on murine
erythroleukemia cell growth at concentrations over 50 microM. The cell proliferation was, however, restored when
canavalmine was removed from the culture medium after 24 h. Treatment of the cells with 500 microM
canavalmine blocked the accumulation of intracellular
polyamines. Especially, both
spermine and
spermidine levels were reduced below 50% of those in control cells after 48 h and below 30% after 96 h. The decreased contents of
spermine and
spermidine were compensated for by the increased content of
canavalmine incorporated within the cells. In these cells,
RNA and
protein contents also decreased. The degree of growth inhibition by
canavalmine during the cell cycle was examined using synchronized cells. Serum-induced growth stimulation was inhibited by
canavalmine most effectively in the cells at G1 phase prior to
DNA synthesis. The antiproliferative effect decreased when
canavalmine was added to the cells after commencement of
DNA synthesis. The results suggest that the growth-inhibitory action of
canavalmine on murine
erythroleukemia cells is most likely due to an inhibition of early events of the cell cycle, possibly due to the interference of a structure-specific function of
spermidine and/or
spermine on DNA replication.