METAPHASE-ARRESTING ACTION OF CARCINOSTATIC TENUAZONIC ACID

Abstract

Carcinostatic 5-benzyl-3-(1'-anilinoethylidene)pyrolidine-2, 4-dione (TN-16) and 5-(p-hydroxybenzyl)-3-(1'-anilinoethylidene)pyrolidine-2, 4-dione (TN-17), structural analogs of tenuazonic acid, showed a remarkable metaphase-arresting effect on Yoshida sarcoma cells in vitro. Minimum effective concentration of TN-16 to arrest tumor cells at metaphase was 0.1μM, which was one-tenth as active as colchicine.
In contrast to colchicine, metaphase-arresting effect of TN-16 and TN-17 was expressed only when the compound was present in the culture medium. Thus Yoshida sarcoma cells arrested at metaphase by TN-16 or TN-17 divided within 1hr after release from the compound.
The fact that the metaphase-arresting action of TN-16 did not compete with colchicine, and colchicine action overcame that of TN-16 suggests that the receptor sites of Yoshida sarcoma cells for the two compounds may be different, or the affinity of TN-16 to the receptor site is weaker than that of colchicine.
Activities of tumor cells to synthesize nucleic acids and protein were not specifically inhibited by TN-16.