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Vol. 53, Issue 3, 402-407, March 1998
B
Institute of Pharmacology, Toxicology, and Pharmacy,
Königinstrasse 16, D-80539 Munich, Germany (V.M.D.,
A.M.V.) and
Department of Medicine II, Klinikum Grosshadern, University
of Munich, D-81377 Munich, Germany (A.L.G.)
The pharmacological role of garlic in prevention and treatment of
cancer 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
induces apoptosis in human leukemic cells, but not in peripheral
mononuclear blood cells of healthy donors. The effect was dose and time
dependent. Apoptosis was judged by three criteria, morphology of cells,
quantification of subdiploid DNA content by flow cytometry, and
detection of DNA fragmentation by gel electrophoresis. Ajoene increased
the production of intracellular peroxide in a dose- and time-dependent
fashion, which could be partially blocked by preincubation of the human
leukemic cells with the antioxidant N-acetylcysteine.
Interestingly, N-acetylcysteine-treated cells showed a
50% loss of ajoene-induced apoptosis. Moreover, ajoene was
demonstrated to activate nuclear translocation of the transcription factor nuclear factor
B, an effect that was abrogated in
N-acetylcysteine-loaded cells. These results suggested
that ajoene might induce apoptosis in human leukemic cells via
stimulation of peroxide production and activation of nuclear factor
B. This is a novel aspect in the biological profile of this garlic
compound and an important step in elucidating the underlying molecular
mechanisms of its antitumor action.
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