Dietary agents that induce
glutathione S-
transferases and related detoxification systems (Phase 2
enzyme inducers) are thought to prevent
cancer by enhancing elimination of chemical
carcinogens. The present study shows that compounds of this group (
benzyl isothiocyanate,
allyl sulfide,
dimethyl fumarate,
butylated hydroxyanisole) activated apoptosis in human colon
carcinoma (HT29) cells in culture over the same concentration ranges that elicited increases in
enzyme activity (5-25, 25-100, 10-100, 15-60 micromol/L, respectively). Pretreatment of cells with
sodium butyrate, an agent that induces HT29 cell differentiation, resulted in parallel increases in Phase 2
enzyme activities and induction of apoptosis in response to the inducers. Cell death characteristics included apoptotic morphological changes, appearance of cells at sub-G1 phase on flow cytometry,
caspase activation, DNA fragmentation and TUNEL-positive staining. The results suggest that dietary Phase 2 inducers may protect against
cancer by a mechanism distinct from and in addition to that associated with enhanced elimination of
carcinogens. If this occurs in vivo, diets high in such compounds could eliminate precancerous cells by apoptosis at time points well after initial exposure to chemical
mutagens and
carcinogens.