In order to elucidate the biochemical basis for the selective cytotoxicity of D-
glucosamine to neoplastic cells, the effect of
glucosamine on the growth and several functions of
mastocytoma P-815 cells were examined. Incubation of
mastocytoma cells with 5 mM
glucosamine resulted in a marked inhibition of growth and a significant reduction of cellular uptake and oxidation of
glucose and of cellular levels of
adenosine triphosphatase (
ATP).
Glucosamine also reduced the
uridine nucleotide pool sizes, and accumulated
uridine diphosphate (
UDP)-
N-acetylglucosamine. However, growth inhibition by
glucosamine, which was reversed by
glucose, was not prevented by exogenous
uridine. In addition,
glucosamine suppressed the phosphorylation of
thymidine and its incorporation into
deoxyribonucleic acid (
DNA). The suppression of cell division by
glucosamine was accompanied by the elevation of several functions of
mastocytoma cells, including the accumulation of adenosine-3', 5'-monophosphate (cAMP),
histamine, and
serotonin. The incorporation of [(35)S]SO(4)(2-) into acidic
glycosaminoglycan was also increased. Of these functional alterations, the elevation of cAMP levels was the earliest detectable change, indicating that growth and functions of
mastocytoma cells are also regulated by cAMP. However,
glucosamine did not affect the
adenylate cyclase activity of plasma membrane in vitro, suggesting the necessity of intact membrane structure for the action of
glucosamine.