At high cytotoxic concentrations, actinomycin D (ActD) blocks transcription, decreasing levels of MDM2 and thus causing p53 stabilization. At low cytostatic concentrations, ActD causes ribosomal stress, which decreases MDM2 activity, resulting in p53 stabilization and activation. ActD can thus be used for p53-based cyclotherapy. We analyzed pathways mediating ActD-induced p53 expression. Inhibi...

Actinomycin, an antibiotic first isolated from a cullture of Streptomyces antibioticus by Waksinan and Woodruff (1940), has since been obtained from fermentations with a number of Streptomyces species. Because of certain differences in the properties of some of the actinomycin products, a series of designations, A, B, C, D, I, J, and X, have been employed to classify them. Each of these substan...

The Antarctic Streptomyces fildesensis has been recognized for its production of antimicrobial compounds with interesting biological activities against foodborne bacteria and multi-resistant strains, but not potential antiproliferative activity mechanisms involved. Two bioactive ethyl acetate extract (EAE) fractions were purified via thin-layer chromatography High-Performance Liquid Chromatogra...

A few studies have been carried out on the intracellular distribution of actinomycin DH all of them at the level of light optical radioautography since the specific activity of the labeled antibiotic did not permit its ultrastructural localization. These studies have shown that actinomycin D-3H is located in the nucleus (1, 4, 8) and is associated with the deoxyribonucleoprotein fraction (10) a...

A modified actinomycin D was prepared with a hydroxyl group that replaced the amino group at the chromophore 2-position, a substitution known to strongly reduce affinity for double-stranded DNA. Interactions of the modified drug on single-stranded DNAs of the defined sequence were investigated. Competition assays showed that 2-hydroxyactinomycin D has low affinity for two oligonucleotides that ...