Mode of Action of Tylocrebrine: Effects on Protein and Nucleic Acid Synthesis

The phenanthrene alkaloid tylocrebrine irreversibly inhibits protein biosynthesis in HeLa cells and rabbit reticulocytes. In HeLa cells, concentrations of tylocrebrine that inhibit protein synthesis by 95% inhibit DNA and RNA synthesis by 75% and 60%, respectively. In contrast to effects on DNA synthesis, inhibition of RNA synthesis is readily reversible. At a concentration of 1 mM, tylocrebrine inhibits RNA polymerase activity in isolated HeLa cell nuclei by 20%. In reticulocyte lysates, tylocrebrine prevents breakdown of polyribosomes and release of nascent peptide chains. Globin synthesis is inhibited by the drug; this inhibition can be partially overcome by increasing the concentration of mercaptoethanol, glutathione, or dithiothreitol. Tylocrebrine does not prevent synthesis of polyphenylalanin on reticulocyte ribosomes, nor does it affect the activities of guanosine triphosphatase and peptidyltransferase. The principal effect of tylocrebrine on protein biosynthesis is on chain elongation.