INVITRO INHIBITION OF HUMAN LEUKEMIC-CELLS (CCRF-CEM) BY AGAROSE-IMMOBILIZED NEOCARZINOSTATIN

Google Scholar
  • 1 January 1977
    • journal article
    • research article
    • Vol. 37  (10) , 3731-3736
Abstract
Neocarzinostatin (NCS) is an acidic protein (MW, 10,700) isolated from Streptomyces carzinostaticus that has antitumor activity in model rodent systems and humans. In vitro it inhibits the growth of a human lymphoblastic leukemic cell line (CCRF-CEM) at a very low concentration (the amount of drug that causes a 50% inhibition of growth compared to control cultures as extrapolated from a dose-response curve (ID50), 2.4 .times. 10-9 M). NCS was covalently coupled to the N-hydroxysuccinimide ester of agarose and a product that, by a variety of biochemical and immunological criteria, was demonstrated to be devoid of any free or loosely bound NCS was obtained. Agarose bound NCS, which is unable to enter cells because of its size, retains a significant amount of inhibitory activity (ID50, 6-15 .times. 10-9 M) and is also capable of inhibiting 3H deoxythymidine incorporation into CCRF-CEM cells. Since agarose bound NCS cannot enter mammalian cells, the above findings indicate that NCS is able to exert its toxic effects by binding to or reacting with receptors on the cell membrane.