Quercetin (Que) has consistently been reported to be useful cytotoxic compound in vivo and in vitro, but little is known on its metabolites. Here, we examined and compared the cytotoxic effects of Que and its water-soluble metabolites, isorhamnetin (IS) and isorhamnetin-3-glucuronide (I3G), in human breast-cancer MCF-7 cells to uncover their tumor-inhibitory mechanisms and structure–function relationships. The results showed that Que, IS, and I3G could dose-dependently inhibit the growth of MCF-7 cells, and the cytotoxic effect was ranked as Que > IS > I3G. Furthermore, Que, IS, and I3G mediated cell-cycle arrest principally in S phase, followed by a decrease in the number of cells in G0/G1 and G2/M; moreover, 70.8, 68.9, and 49.8% of MCF-7 tumor cells entered early-phase apoptosis when treated with 100 μM Que, IS, and I3G for 48 h, respectively. Moreover, induction of apoptosis by Que, IS, and I3G was accompanied by the marginal generation of intracellular reactive oxygen species (ROS). Given these results, Que, IS, and I3G possess strong cytotoxic effects through an ROS-dependent apoptosis pathway in MCF-7 cells.

中文翻译：

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槲皮素及其两种衍生物异鼠李素和异鼠李素-3-葡萄糖醛酸苷在抑制人乳腺癌MCF-7细胞增殖中的差异作用

槲皮素（Que）一直被报道在体内和体外都是有用的细胞毒性化合物，但对其代谢产物知之甚少。在这里，我们检查并比较了Que及其水溶性代谢产物异鼠李素（IS）和异鼠李素-3-葡萄糖醛酸（I3G）在人乳腺癌MCF-7细胞中的细胞毒性作用，从而揭示了它们的抑瘤机制和结构–功能关系。结果表明，Que，IS和I3G可以剂量依赖性地抑制MCF-7细胞的生长，其细胞毒性作用为Que> IS> I3G。此外，Que，IS和I3G介导的细胞周期停滞主要在S期，随后G0 / G1和G2 / M中的细胞数量减少。此外，当用100μMQue，IS和I3G处理48小时后，有70.8、68.9和49.8％的MCF-7肿瘤细胞进入了早期凋亡状态，分别。此外，由Que，IS和I3G诱导的细胞凋亡伴随着细胞内活性氧（ROS）的少量生成。鉴于这些结果，Que，IS和I3G通过​​MCF-7细胞中的ROS依赖性凋亡途径具有强大的细胞毒性作用。