Auf'm Hennekamp 50, 40225 Düsseldorf, Germany.
Anticancer Res. 2009 Nov;29(11):4657-64.
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.
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.
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.
We conclude that AhR is only marginally involved in the antileukemic effects of its ligand curcumin.
急性髓系白血病（AML）仍然存在着严峻的治疗挑战，因为总体而言，患者的长期生存预后仍然很差。具有抗白血病特性的天然植物衍生物质提供了新的治疗可能性，或者可以作为旁观者治疗。它们的作用机制在分子水平上往往并不完全清楚，这限制了基于理论的筛选和应用策略。植物物质姜黄素是转录因子芳烃受体（AhR）的已知激活剂，并且具有很好的抗白血病作用。AhR 调节细胞过程，包括细胞周期和细胞凋亡。我们在这里询问姜黄素对 AhR 的直接激活是否有助于其抗白血病/凋亡潜能。
测量半胱天冬酶 3/7、8 和 9 的诱导、线粒体跨膜电位的破坏、BCL-2/BAX 比值以及细胞的 DNA 含量，作为细胞凋亡的指标。此外，还评估了细胞周期抑制剂 p21 和 p27 的诱导。
虽然在 HL-60 细胞中证实了姜黄素对 AhR 信号的触发，但两种 AhR 拮抗剂，α-萘黄酮（alphaNF）和 3'-甲氧基-4'-硝基黄酮（MNF）并未阻断上述凋亡参数的诱导。仅检测到 AhR 依赖性半胱天冬酶 3/7 的适度（20%）诱导。有趣的是，姜黄素和抗癌 1,25-二羟基维生素 D3 诱导的转录变化有三分之一的重叠。
我们得出结论，AhR 仅在其配体姜黄素的抗白血病作用中起很小的作用。
