Quercetin-induced apoptotic cascade in cancer cells: Antioxidant versus estrogen receptor α-dependent mechanisms
Quercetin-induced apoptotic cascade in cancer cells: Antioxidant versus estrogen receptor α-dependent mechanisms
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DOI：
10.1002/mnfr.200800239
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发表时间：
2009-06-01
影响因子：
5.2
通讯作者：
Marino, Maria
中科院分区：
文献类型：
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作者：
Galluzzo, Paola;Martini, Chiara;Marino, Maria
黄酮醇槲皮素，特别是在苹果，葡萄酒和洋葱中含量丰富，据报道在许多癌细胞系中具有抗增殖作用。抗氧化或促氧化活性和激酶抑制已被提出作为这些作用的分子机制。此外，已观察到雌激素活性，但目前尚不清楚后者活性是否在槲皮素诱导的抗增殖作用中发挥作用。在这里，我们研究了槲皮素在缺乏或含有转染的雌激素受体α（ER α;即，人宫颈上皮样癌HeLa细胞）。虽然没有测试的槲皮素浓度增加活性氧（ROS）在HeLa细胞中的产生，槲皮素刺激阻止H2 O2诱导的ROS的产生在ER α的存在和不存在。然而，这种类黄酮诱导p38/MAPK的活化，导致促凋亡半胱天冬酶-3活化和聚（ADP-核糖）聚合酶切割仅在ER α存在下。值得注意的是，没有下调存活激酶（即，AKT和ERK）。总之，这些发现表明槲皮素通过ER α依赖性机制导致HeLa细胞死亡，该机制涉及半胱天冬酶和p38激酶激活。这些发现表明黄酮类化合物对癌症生长的新的潜在化学预防作用。
The flavonol quercetin, especially abundant in apple, wine, and onions, is reported to have anti-proliferative effects in many cancer cell lines. Antioxidant or pro-oxidant activities and kinase inhibition have been proposed as molecular mechanisms for these effects. In addition, an estrogenic activity has been observed but, at the present, it is poorly understood whether this latter activity plays a role in the quercetin-induced anti-proliferative effects. Here, we studied the molecular mechanisms of quercetin committed to the generation of an apoptotic cascade in cancer cells devoid or containing transfected estrogen receptor a (ER alpha; i.e., human cervix epitheloid carcinoma HeLa cells). Although none of tested quercetin concentrations increase reactive oxygen species (ROS) generation in HeLa cells, quercetin stimulation prevents the H2O2-induced ROS production both in the presence and in the absence of ER alpha. However, this flavonoid induces the activation of p38/MAPK, leading to the proapoptotic caspase-3 activation and to the poly(ADP-ribose) polymerase cleavage only in the presence of ER alpha. Notably, no down-regulation of survival kinases (i.e., AKT and ERK) was reported. Taken together, these findings Suggest that quercetin results in HeLa cell death through an ER alpha-dependent mechanism involving caspase- and p38 kinase activation. These findings indicate new potential chemopreventive actions of flavonoids on cancer growth.