alpha-sarcin and Sarcoma-180

Isolation and purification procedures are given for the new antitumor agent, alpha sarcin. These procedures include the use of column ion exchange with a carboxylic resin (Amberlite IRC50), dialysis, decolorization with activated charcoal, gradient salt chromatography, salt removal, and drying from the frozen state. The final product has an activity of 800 sarcoma 180 mouse dilution units per mg. The amino acid composition of the purified material is reported. All of the usual amino acids found in proteins were present except methionine. In addition to the usual amino acids, an unknown amino acid was present in the acid hydrolysate. The latter was isolated, and was found to yield phenylalanine and kynurenine. This compound, which has been named "sarcinine," is extremely stable in 6 n hydrochloric acid in the absence of air, and is unstable in alkali. Sarcinine has also been found in two other antitumor peptides produced by aspergilli, and so may relate significantly to the antitumor properties of these peptides.

Topics: Amino Acids; Animals; Antineoplastic Agents; Aspergillus; Biological Assay; Chemical Phenomena; Chemistry; Chromatography; Culture Media; Endoribonucleases; Fermentation; Fungal Proteins; Hot Temperature; Hydrogen-Ion Concentration; Kynurenine; Methionine; Mice; Peptides; Pharmacology; Phenylalanine; Proteins; Renal Dialysis; Research; Sarcoma 180; Spectrum Analysis; Toxicology

Aspergillus giganteus MDH 18894 was found to produce alpha sarcin, a new antitumor agent inhibitory to a number of different animal tumors. This culture produced culture filtrates that inhibited mouse sarcoma 180 at dilutions up to 1:32. Optimal fermentation conditions were established for shake flasks and 30-liter and 100-gal (378.5-liter) fermentors. Results from a variety of media were reported; however, the medium which yielded the most reproducible filtrates consisted of 2% corn starch, 1.5% beef extract (Difco), 2% peptone (Difco), and 0.5% sodium chloride. Purified preparations of 800 sarcoma 180 dilution units per mg were inactive against bacteria, yeasts, molds, actinomycetes, and protozoa, but were cytotoxic to several strains of mammalian cells. Alpha sarcin inhibited sarcoma 180 in mice at a dose of 62.5 mug per kg per day. A variety of other animal tumors were also inhibited by this compound.

Topics: Animals; Antineoplastic Agents; Aspergillus; Biological Assay; Culture Media; Endoribonucleases; Fermentation; Fungal Proteins; Mice; Neoplasms, Experimental; Peptones; Pharmacology; Research; Sarcoma 180; Sodium Chloride; Starch; Toxicology