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  • Title: The arylhydrocarbon receptor is only marginally involved in the antileukemic effects of its ligand curcumin.
    Author: Goergens A, Frericks M, Esser C.
    Journal: Anticancer Res; 2009 Nov; 29(11):4657-64. PubMed ID: 20032417.
    Abstract:
    BACKGROUND: Acute myeloid leukaemia (AML) continues to present demanding treatment challenges, as in general the prognosis for long-term survival remains dire for the patients. Natural plant-derived substances with antileukemic properties offer new treatment possibilities or may act as by-stander therapy. Their molecular mechanisms of action are often not entirely clear, limiting theory-directed screening and application strategies. The plant substance curcumin is a known activator of the transcription factor aryl hydrocarbon receptor (AhR), and has well-documented antileukemic effects. The AhR regulates cell processes, including cell cycle and apoptosis. We ask here whether direct AhR-activation by curcumin contributes to its antileukemic/apoptotic potential. MATERIALS AND METHODS: The induction of caspases 3/7, 8, and 9, the breakdown of mitochondrial transmembrane potential, the BCL-2/BAX ratio, and the DNA content of cells were measured as indicators of apoptosis. In addition, the induction of cell cycle inhibitors p21 and p27 were assessed. RESULTS: While triggering of AhR signalling by curcumin in HL-60 cells was confirmed, induction of the above apoptosis parameters was not blocked by two AhR antagonists, alpha-naphtoflavone (alphaNF) and 3'-methoxy-4'nitroflavone (MNF). Only a moderate (20%) AhR-dependent induction of caspases 3/7 was detectable. Interestingly, transcriptional changes induced by curcumin and by anticarcinogenic 1,25-dihydroxy vitamin D3 overlapped by one third. CONCLUSION: We conclude that AhR is only marginally involved in the antileukemic effects of its ligand curcumin.
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