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

Ascofuranone (AF) has antitumor protective property on experimental tumors. We examined the action of AF on lymphoma L5178Y to explore the mechanism of the antitumor activity. AF completely prevented the growth of L5178Y at 25 micrograms/ml cytostatically. The compound exhibited general inhibitory effects on the macromolecular syntheses. Among them, protein synthesis was most severely inhibited by AF and to the same extent as by cycloheximide. AF, however, did not affect protein synthesis by 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. Especially, the incorporation of 14C]acetate into squalene was almost completely blocked at 25 micrograms/ml. The incorporation of 14C]acetate into triglyceride was inhibited and that into cholesterol was enhanced. Concerning the diglycerides, the incorporation of 14C]acetate was enhanced and that of 3H]glycerol was inhibited. The incorporation of 3H]glycerol and 3H]mevalonate into the intact cell was significantly inhibited as compared with 14C]acetate. As those effects were not observed with cycloheximide, they were suggested to be characteristic of AF. AF inhibited hypotonic hemolysis. In contrast, hemolysis by deoxycholate was stimulated. Possible mechanism of the antitumor activity of AF is discussed.