Combination of quercetin and hyperoside has anticancer effects on renal cancer cells through inhibition of oncogenic microRNA-27a
Combination of quercetin and hyperoside has anticancer effects on renal cancer cells through inhibition of oncogenic microRNA-27a
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槲皮素和金丝桃苷的组合通过抑制致癌的 microRNA-27a 对肾癌细胞具有抗癌作用
DOI：
10.3892/or.2013.2811
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发表时间：
2014-01-01
期刊：
影响因子：
4.2
通讯作者：
Zheng, Jun-Hua
中科院分区：
文献类型：
--
作者：
Li, Wei;Liu, Min;Zheng, Jun-Hua
槲皮素和金丝桃苷 (QH) 组合（1:1 比例）先前已被证明可以抑制人类白血病细胞的生长。在这里，我们研究了相同混合物在 786-O 肾癌细胞中的抗癌活性。在 786-O 细胞 (3.8-60 g/ml) 中，QH 使活性氧 (ROS) 的产生减少高达 2.25 倍，抗氧化能力增加高达 3 倍，而活力的 IC50 值分别为 18.2、18.7 和 11.8 g/ml。 QH 还诱导 caspase-3 裂解（2 倍）并增加 PARP 裂解。特异性蛋白 (Sp) 转录因子在癌细胞中过度表达，并调节细胞增殖、存活和血管生成所需的基因。 QH 处理降低了 Sp1、Sp3 和 Sp4 mRNA 的表达，并且伴随着蛋白质表达的降低。此外，Sp依赖性抗凋亡存活基因survivin的表达在mRNA和蛋白质水平上也显着降低。 QH 减少 microRNA-27a (miR-27a) 并诱导锌指蛋白 ZBTB10（一种 Sp 阻遏蛋白），表明 QH 与 miR-27a-ZBTB10 轴之间的相互作用在 Sp 下调中发挥作用。用 miR-27a 的特异性模拟物转染细胞证实了这一点，部分逆转了 QH 的影响。这些发现与之前关于结肠癌细胞中植物抗癌剂的研究一致。
Quercetin and hyperoside (QH) in combination (1:1 ratio) have previously been shown to inhibit the growth of human leukemia cells. Here, we investigated the anticancer activity of the same mixture in 786-O renal cancer cells. QH decreased the generation of reactive oxygen species (ROS) by up to 2.25-fold and increased the antioxidant capacity by up to 3-fold in 786-O cells (3.8-60 g/ml), whereas IC50 values for viability were 18.2, 18.7 and 11.8 g/ml, respectively. QH also induced caspase-3 cleavage (2-fold) and increased PARP cleavage. Specificity protein (Sp) transcription factors are overexpressed in cancer cells and regulate genes required for cell proliferation, survival and angiogenesis. QH treatment decreased the expression of Sp1, Sp3 and Sp4 mRNA and this was accompanied by decreased protein expression. Moreover, expression of the Sp-dependent anti-apoptotic survival gene survivin was also significantly reduced, both at the mRNA and protein levels. QH decreased microRNA-27a (miR-27a) and induced the zinc finger protein ZBTB10, an Sp-repressor, suggesting that interactions between QH and the miR-27a-ZBTB10 axis play a role in Sp downregulation. This was confirmed by transfection of cells with a specific mimic for miR-27a, which partially reversed the effects of QH. These findings are consistent with previous studies on botanical anticancer agents in colon cancer cells.