Chemopreventive Isothiocyanates Induce Apoptosis and Caspase-3-like Protease Activity

摘要: Isothiocyanates exert strong anticarcinogenic effects in a number of animal models cancer, presumably by modulation xenobiotic-metabolizing enzymes, such as inhibition cytochrome P-450 and/or induction phase II detoxifying enzymes. Here, we report that phenethyl isothiocyanate and other structurally related isothiocyanates, phenylmethyl isothiocyanate, phenylbutyl phenylhexyl but not phenyl induced apoptosis HeLa cells time- dose-dependent manner. Treatment with apoptosis-inducing concentrations isothiocyanates also caused rapid transient caspase-3/CPP32-like activity. Furthermore, these except stimulated proteolytic cleavage poly-(ADP-ribose) polymerase, which followed the appearance caspase activity preceded DNA fragmentation. Pretreatment potent caspase-3 inhibitor acetyl-Asp-Glu-Val-Asp-aldehyde inhibited isothiocyanate-induced caspase-3-like apoptosis. These results suggest may induce through caspase-3-dependent mechanism. The provide distinct mechanism for their chemopreventive functions.