Effects of an antitumor agent, ascofuranone, on the macromolecular syntheses of intact cells.

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Abstract
Ascofuranone (AF) has an antitumor protective property on experimental tumors. The action of AF on lymphoma L5178Y was examined to explore the mechanism of the antitumor activity. AF completely prevented the growth of L5178Y at 25 .mu.g/ml cytostatically. The compound exhibited general inhibitory effects on the macromolecular syntheses. Protein synthesis was most severely inhibited by AF and to the same extent as by cycloheximide. AF did not affect protein synthesis by a cell-free system, even at 2 mg/ml. Although AF inhibited the incorporation of [14C]acetate into total acid precipitable products only slightly, the synthetic pattern of simple lipids from [14C]acetate was significantly changed. The incorporation of [14C]acetate into squalene was almost completely blocked at 25 .mu.g/ml. The incorporation of [14C]acetate into triglyceride was inhibited and that into cholesterol was enhanced. The incorporation of [14C]acetate into diglycerides was enhanced and that of [3H]glycerol was inhibited. The incorporation of [3H]glycerol and [3H]mevalonate into the intact cell was significantly inhibited compared to [14C]acetate. As those effects were not observed with cycloheximide, they may be characteristic of AF. AF inhibited hypotonic hemolysis. Hemolysis by deoxycholate was stimulated. The possible mechanism of the antitumor activity of AF is discussed.