Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Food Funct. 2018 May 23;9(5):2809-2819. doi: 10.1039/c8fo00054a.
Ginnalin A (also known as acertannin) is one of the most important phenolic compounds of several beverage Acer plants. In this study, it is reported for the first time that ginnalin A is an activator of the Nrf2 signaling pathway in human colon cancer cells. Ginnalin A, isolated from the leaves of Acer tataricum subsp. ginnala, exhibited promising preventive activity against colon cancer cells (HCT116, SW480 and SW620) with IC50 values of 24.8 μM, 22.0 μM and 39.7 μM, respectively. In addition, it significantly reduced the colony formation of these cells. Flow cytometry analysis indicated that ginnalin A suppressed cancer proliferation via the induction of cell cycle arrest at the S-phase. Real time PCR analysis demonstrated that ginnalin A can upregulate the mRNA expression levels of Nrf2-related antioxidant genes Nrf2, HO-1 and NQO1. Western blotting analysis revealed that ginnalin A promoted the Nrf2 nuclear translocation and upregulated the proteins Nrf2, HO-1 and NQO1. Moreover, the upregulation of p62 and the inhibition of Keap1 were also found by Western blotting analysis. Therefore, the activation of the Nrf2 signaling pathway was probably induced through the upregulation of p62 and the inhibition of Keap1.
金纳林 A（也称为 acertannin）是几种饮料 Acer 植物中最重要的酚类化合物之一。在这项研究中，首次报道金纳林 A 是人类结肠癌细胞中 Nrf2 信号通路的激活剂。金纳林 A 从 Acer tataricum subsp. ginnala 的叶子中分离出来，对结肠癌细胞（HCT116、SW480 和 SW620）表现出有希望的预防活性，IC50 值分别为 24.8 μM、22.0 μM 和 39.7 μM。此外，它还显著降低了这些细胞的集落形成。流式细胞术分析表明，金纳林 A 通过诱导细胞周期停滞在 S 期来抑制癌细胞增殖。实时 PCR 分析表明，金纳林 A 可以上调 Nrf2 相关抗氧化基因 Nrf2、HO-1 和 NQO1 的 mRNA 表达水平。Western blotting 分析显示，金纳林 A 促进了 Nrf2 的核转位，并上调了 Nrf2、HO-1 和 NQO1 的蛋白表达。此外，Western blotting 分析还发现 p62 的上调和 Keap1 的抑制。因此，Nrf2 信号通路的激活可能是通过 p62 的上调和 Keap1 的抑制来诱导的。
