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

W G Kirlin1, J Cai, M J DeLong

  • 1Department of Biochemistry, Winship Cancer Center, Emory University, Atlanta, GA 30322, USA.

The Journal of Nutrition
|September 28, 1999
PubMed

Insights

Dietary compounds that boost detoxification enzymes (Phase 2 inducers) also trigger cancer cell death (apoptosis). This suggests a dual mechanism for cancer prevention beyond just eliminating carcinogens.

Area of Science:

  • Oncology
  • Biochemistry
  • Molecular Biology

Background:

  • Dietary agents inducing Phase 2 enzymes are known for cancer chemoprevention via enhanced carcinogen elimination.
  • The precise mechanisms by which these dietary agents exert protective effects require further elucidation.

Purpose of the Study:

  • To investigate whether dietary Phase 2 enzyme inducers can directly induce apoptosis in human colon carcinoma cells.
  • To explore the relationship between Phase 2 enzyme induction and apoptosis in cancer cells.

Main Methods:

  • Human colon carcinoma (HT29) cells were treated with various Phase 2 inducers (benzyl isothiocyanate, allyl sulfide, dimethyl fumarate, butylated hydroxyanisole).
  • Apoptosis was assessed through morphological changes, flow cytometry (sub-G1 phase), caspase activation, DNA fragmentation, and TUNEL staining.
  • Cells were pretreated with sodium butyrate to induce differentiation and assess its effect on enzyme activity and apoptosis.

Main Results:

  • Several dietary Phase 2 inducers activated apoptosis in HT29 cells within concentration ranges that increased enzyme activity.
  • Sodium butyrate pretreatment enhanced both Phase 2 enzyme activity and the induction of apoptosis by these agents.
  • Confirmed apoptotic characteristics, including DNA fragmentation and caspase activation, were observed.

Conclusions:

  • Dietary Phase 2 inducers possess a potential cancer-protective mechanism involving direct induction of apoptosis in cancer cells, independent of enhanced carcinogen elimination.
  • This suggests that diets rich in these compounds may eliminate precancerous cells via apoptosis, offering a broader protective strategy against cancer development.

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