Prolonged inhibition of protein and glycoprotein synthesis in tumor cells treated with muconomycin A

Abstract

Several agents were compared for their ability to inhibit protein synthesis for long periods in tumor cells growing in culture. Mouse B16 melanoma cells, treated with high concentrations of cycloheximide or pactamycin for 1 hour and then washed repeatedly, recovered their ability to incorporate [3H]leucine into protein in about 4 hours, while cells treated with emetine recovered in 12 hours. After similar treatment with muconomycin A, however, incorporation of [3H]leucine remained inhibited for at least 30 hours. During this time the cells remained attached to the culture dishes, were able to exclude trypan blue dye, and retained nearly normal levels of rubidium-86 content. When another, untreated, population of cells was added to the muconomycin-treated cells, protein synthesis was not inhibited in the untreated population; action of the drug was thus shown to be confined to the treated cells. In melanoma cells treated with neuraminidase and muconomycin, measurement of glycoprotein synthesis (as determined by sialic acid analysis) showed that muconomycin also inhibited restoration of sialic acid content. Brief treatment with muconomycin, therefore, appeared to be sufficient for prolonged inhibition of protein and glycoprotein synthesis.