Effects of the spermine analogue canavalmine on proliferation of murine erythroleukemia cells in culture.
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.
D000818:Animals; D002172:Canavanine / Q000008:administration & dosage / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D004273:DNA, Neoplasm / Q000378:metabolism; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism; D011073:Polyamines / Q000378:metabolism
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D011073:Polyamines; D002172:Canavanine