Production and biological activity of rebeccamycin, a novel antitumor agent.
An actinomycete, strain C-38,383, was selected in a screening program for the isolation of novel antitumor agents. A yellow crystalline product, named rebeccamycin, was isolated from the mycelium and was found to have activity against P388 leukemia, L1210 leukemia and B16 melanoma implanted in mice. Rebeccamycin inhibits the growth of human lung adenocarcinoma cells (A549) and produces single-strand breaks in the DNA of these cells. No DNA-protein cross-links were detected. A related antibiotic, staurosporine, is produced by Streptomyces staurosporeus and Streptomyces actuosus. Strain C-38,383 was found to resemble closely strains of Nocardia aerocolonigenes recently renamed Saccharothrix aerocolonigenes. A strain selection isolate without aerial mycelium, C-38,383-RK-1, failed to produce rebeccamycin while a strain with aerial mycelium, C-38,383-RK-2, was found to be a suitable strain for production. A description of the producing strain is presented and its taxonomic position is reviewed. A fermentor containing 37 liters of production medium gave a rebeccamycin yield of 663 mg/liter after 204 hours of incubation with strain C-38,383-RK-2.
D000192:Actinomycetales / Q000032:analysis* / Q000145:classification / Q000502:physiology; D000230:Adenocarcinoma / Q000188:drug therapy; D000617:Aminoglycosides; D000818:Animals; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic / Q000302:isolation & purification* / Q000494:pharmacology; D002227:Carbazoles; D050260:Carbohydrate Metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology; D004249:DNA Damage; D006027:Glycosides / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007211:Indoles; D007364:Intercalating Agents; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D008826:Microbial Sensitivity Tests; D016685:Mitomycin; D008937:Mitomycins / Q000494:pharmacology; D009696:Nucleic Acids / Q000096:biosynthesis; D014176:Protein Biosynthesis
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D002227:Carbazoles; D006027:Glycosides; D007211:Indoles; D007364:Intercalating Agents; D008937:Mitomycins; D009696:Nucleic Acids; D016685:Mitomycin; C053339:rebeccamycin; D002945:Cisplatin