Antitumor agents LXIII: the effects of microlenin on nucleic acid and protein syntheses of Ehrlich ascites cells.

Microlenin, a novel dimeric sesquiterpene lactone isolated from Texas Helenium microcephalum, was shown to inhibit Ehrlich ascites carcinoma growth. Metabolic studies demonstrated that DNA synthesis and protein synthesis were significantly inhibited by two doses of microlenin at 5 mg/kg/day. DNA synthesis appeared to be blocked at several sites including DNA polymerase, purine synthesis, and dihydrofolate reductase. Thymidine nucleotide pools were significantly reduced by microlenin. Protein synthesis inhibition by microlenin appeared to occur during the initiation step of polypeptide synthesis. The metabolic effects of microlenin were similar to other sesquiterpene lactones in the Ehrlich ascites carcinoma cells. However, a lower dose of microlenin was required to bring about these metabolic effects when compared with other sesquiterpene lactones. Thus, microlenin may be a more likely therapeutic agent than helenalin which has demonstrated cellular toxicity.