Effect of D-glucosamine on growth and several functions of cultured mastocytoma P-815 cells.

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.