Ethyl 4-isothiocyanatobutanoate--antiproliferative activity in vitro and in vivo

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