Phenethyl isothiocyanate triggers apoptosis in jurkat cells made resistant by the overexpression of Bcl-2

Abstract

Isothiocyanates are a class of naturally occuring chemopreventive agents known to be effective at triggering apoptosis. In this study, we show that whereas overexpression of the oncoprotein Bcl-2 renders Jurkat T-lymphoma cells resistant to a range of cytotoxic agents, phenethyl isothiocyanate is able to overcome the inhibitory action of Bcl-2 and trigger apoptosis. A 50-fold increase in Bcl-2 expression shifted the dose-response curve, with an increase in the phenethyl isothiocyanate LD 50 from 7 to 15 μmol/L, but there was still a complete loss in cell viability at doses in excess of 20 μmol/L. At these concentrations, cytotoxicity was strongly associated with caspase activation, phosphati..