Ajoene, a compound of garlic, induces apoptosis in human promyeloleukemic cells, accompanied by generation of reactive oxygen species and activation of nuclear factor kappaB.
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 kappaB, 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 kappaB. 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.
Dirsch
V M
VM
Institute of Pharmacology, Toxicology, and Pharmacy, Koniginstrasse 16, D-80539 Munich, Germany.
Gerbes
A L
AL
Vollmar
A M
AM
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053938:DNA Fragmentation; D004220:Disulfides / Q000494:pharmacology*; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013454:Sulfoxides
D000970:Antineoplastic Agents; D004220:Disulfides; D016328:NF-kappa B; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D013454:Sulfoxides; C048980:ajoene