ETHYL 4-ISOTHIOCYANATOBUTANOATE - ANTIPROLIFERATIVE ACTIVITY IN-VITROAND IN-VIVO

A new isothiocyanate (ITC) derivate ethyl 4-isothiocyanatobutanoate (E -4IB) induces an immediate dose-dependent inhibitory action on the div ision of HeLa cells in the concentration range 1.0-0.1 mg/l. Concomita nt with the decrease in cell proliferation which follows E-4IB treatme nt the protein:cell number ratio increases and DNA accumulates. Cells which have lost their ability to divide do not stop their glucose meta bolism and only partly stop their glutamine metabolism. The increased content of DNA suggests that cells synthesize DNA without entering int o mitosis and that dying cells are in late S or G2 phases prior to dea th. E-4IB produces a significant growth inhibition of transplanted sar coma cells B77-RF in rats (at 28 mg/kg). A 57% regression in tumor vol ume was observed for at least 30 days following the completion of the in vivo treatment. These findings support the presumption that E-4IB i s a potential anti-cancer drug. However, further studies are needed fo r the optimization of its in vivo activity.