AJOENE, A COMPOUND OF GARLIC, INDUCES APOPTOSIS IN HUMAN PROMYELOLEUKEMIC CELLS, ACCOMPANIED BY GENERATION OF REACTIVE OXYGEN SPECIES AND ACTIVATION OF NUCLEAR FACTOR KAPPA-B

The pharmacological role of garlic in prevention and treatment of canc er has received increasing attention, but thorough investigations into the molecular mechanisms of action of garlic compounds are rare. The present study demonstrates that ajoene, a major compound of garlic ind uces apoptosis in human leukemic cells, but not in peripheral mononucl ear blood cells of healthy donors. The effect was dose and time depend ent. Apoptosis was judged by three criteria, morphology of cells, quan tification of subdiploid DNA content by flow cytometry , and detection of DNA fragmentation by gel electrophoresis. Ajoene increased the pro duction of intracellular peroxide in a dose-and time-dependent fashion , which could be partially blocked by preincubation of the human leuke mic cells with the antioxidant N-acetylcysteine. Interestingly, N-acet ylcysteine-treated cells showed a 50% loss of ajoene-induced apoptosis . Moreover, ajoene was demonstrated to activate nuclear translocation of the transcription factor nuclear factor kappa B, an effect that was abrogated in N-acetylcysteine-loaded cells. These results suggested t hat ajoene might induce apoptosis in human leukemic cells via stimulat ion of peroxide production and activation of nuclear factor kappa B. T his is a novel aspect in the biological profile of this garlic compoun d and an important step in elucidating the underlying molecular mechan isms of its antitumor action.