Unidad de Bioquímica y Biología Molecular, Departamento de Biología de Sistemas, Facultad de Medicina y Ciencias de la Salud, Campus Universitario, Universidad de Alcalá, 28871, Alcalá de Henares, Madrid, Spain.
Unidad de Bioquímica y Biología Molecular, Departamento de Biología de Sistemas, Facultad de Medicina y Ciencias de la Salud, Campus Universitario, Universidad de Alcalá, 28871, Alcalá de Henares, Madrid, Spain.
Chem Biol Interact. 2018 Oct 1;294:158-166. doi: 10.1016/j.cbi.2018.08.015. Epub 2018 Aug 30.
Esculetin (6,7-dihydrocoumarin) and the flavonoid quercetin (3,5,7,3',4' pentahydroxyflavone) are compounds that could change the balance of redox homeostasis. NB4 leukemia cells were treated with 25 μM quercetin for 24 h and with esculetin at either 100 or 500 μM for different times. Quercetin increased the levels of pro-inflammatory NFkB p65 in the nucleus correspondingly reducing them in the cytosol. The levels of NFkB p65 decreased in the nucleus at high esculetin concentration treatments for long times (19 h), concomitantly increasing the levels of anti-inflammatory NFkB p50 in the nucleus. This could suggest formation of inhibitory p50 homodimers possibly related with anti-inflammatory response. Lipoxygenase expression was reduced either by esculetin or quercetin. A significant increase of Nrf2 in the nucleus of NB4 cells treated with 100 μM esculetin for 19 h was observed. Quercetin increased the levels of Nrf2 in the cytosol reducing them in the nucleus. Superoxide dismutase expression increased in NB4 cells treated with esculetin in contrast with quercetin. All these data support a relevant differential role for NFkB and Nrf2 in anti-inflammatory and redox response when apoptosis was induced by esculetin or quercetin in human leukemia NB4 cells.
七叶苷（6,7-二羟香豆素）和黄酮类化合物槲皮素（3,5,7,3',4'五羟基黄酮）是能够改变氧化还原平衡的化合物。用 25µM 槲皮素处理 NB4 白血病细胞 24 小时，用 100 或 500µM 七叶苷处理不同时间。槲皮素相应地增加了核内促炎 NFkB p65 的水平，同时减少了胞浆中的 NFkB p65 水平。在高浓度七叶苷（19 小时）处理下，核内 NFkB p65 水平降低，同时核内抗炎 NFkB p50 水平增加。这可能表明形成了抑制性 p50 同源二聚体，可能与抗炎反应有关。脂氧合酶的表达被七叶苷或槲皮素降低。在用 100µM 七叶苷处理 19 小时后，NB4 细胞的核内 Nrf2 显著增加。槲皮素增加了胞浆中 Nrf2 的水平，同时减少了核内的 Nrf2 水平。超氧化物歧化酶的表达在用七叶苷处理的 NB4 细胞中增加，而在用槲皮素处理的细胞中则减少。所有这些数据支持在人类白血病 NB4 细胞中，七叶苷或槲皮素诱导细胞凋亡时，NFkB 和 Nrf2 在抗炎和氧化还原反应中具有重要的差异作用。
