Pre-neocarzinostatin, a specific antagonist of neocarzinostatin.

Abstract

Streptomyces carzinostaticus produces the antitumor protein, NCS, and at the same time a related protein which antagonizes the antimicrobial effect of NCS. This has been designated pre-neocarzinostatin (pre-NCS). The physicochemical properties of pre-NCS are very close to those of NCS, except for a difference in isoelectric point. Production of pre-NCS in the culture filtrate precedes production of NCS. Pre-NCS has no antimicrobial and antitumor effect but antagonizes NCS activity.Pre-NCS, when given 2 hours prior to NCS, markedly diminishes the NCS-induced inhibition of Sarcina lutea growth and DNA synthesis in HeLa cells. However, the antagonistic action of pre-NCS is lost when pre-NCS is washed out from HeLa cell culture after 2 hours incubation. When pre-NCS was given intraperitoneally to mice bearing Sarcoma 180 ascites tumor, subsequent treatment with NCS failed to inhibit the tumor growth. On the other hand, the acute toxicity of NCS given intravenously was not abolished by preceding intravenous injection of pre-NCS.The acute toxicity of pre-NCS by intravenous injection was greater than 100mg/kg in mice.