Dietary compounds that induce cancer preventive phase 2 enzymes activate apoptosis at comparable doses in HT29 colon carcinoma cells

Dietary agents that induce glutathione S-transferases and related detoxific ation systems (Phase 2 enzyme inducers) are thought to prevent cancer by en hancing elimination of chemical carcinogens. The present study shows that c ompounds of this group (benzyl isothiocyanate, allyl sulfide, dimethyl fuma rate, butylated hydroxyanisole) activated apoptosis in human colon carcinom a (HT29) cells in culture over the same concentration ranges that elicited increases in enzyme activity (5-25, 25-100, 10-100, 15-60 mu mol/L, respect ively). Pretreatment of cells with sodium butyrate, an agent that induces H T29 cell differentiation, resulted in parallel increases in Phase 2 enzyme activities and induction of apoptosis in response to the inducers. Cell dea th characteristics included apoptotic morphological changes, appearance of cells at sub-G1 phase on flow cytometry, caspase activation, DNA fragmentat ion and TUNEL-positive staining. The results suggest that dietary Phase 2 i nducers may protect against cancer by a mechanism distinct from and in addi tion to that associated with enhanced elimination of carcinogens. If this o ccurs in vivo, diets high in such compounds could eliminate precancerous ce lls by apoptosis at time points well after initial exposure to chemical mut agens and carcinogens.