The triterpenoid corosolic acid blocks transformation and epigenetically reactivates Nrf2 in TRAMP-C1 prostate cells.
The triterpenoid corosolic acid blocks transformation and epigenetically reactivates Nrf2 in TRAMP-C1 prostate cells.
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DOI：
10.1002/mc.22776
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发表时间：
2018-04
影响因子：
4.6
通讯作者：
Kong AN
中科院分区：
文献类型：
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作者：
Yang J;Wu R;Li W;Gao L;Yang Y;Li P;Kong AN
科罗索酸（Corosolic acid，CRA）存在于各种植物中，在世界范围内被用作健康食品补充剂。尽管有报道称CRA具有显著的抗癌活性，但该化合物对前列腺癌的作用仍不清楚。在这项研究中，我们研究了CRA对细胞转化和核因子红细胞2相关因子2（Nrf 2）通过表观遗传调控在TRAMP-C1前列腺细胞中的再激活的影响。具体而言，我们发现CRA抑制前列腺癌TRAMP-C1细胞的锚定非依赖性生长，但不抑制Nrf 2敲除前列腺癌TRAMP-C1细胞。此外，CRA诱导Nrf 2、血红素加氧酶-1（HO-1）和醌氧化还原酶-1（NQO 1）的mRNA和蛋白表达。硫酸氢盐基因组测序和甲基化DNA免疫沉淀结果显示，CRA处理降低了Nrf 2启动子前5个CpG位点的甲基化水平。使用染色质免疫沉淀（ChIP）测定分析组蛋白修饰，其揭示CRA处理增加组蛋白H3赖氨酸27（H3 K27 ac）的乙酰化，同时减少Nrf 2的启动子区域中组蛋白H3赖氨酸27（H3 K27 me 3）的三甲基化。此外，CRA处理减弱了DNA甲基转移酶（DNMT）和组蛋白脱乙酰酶（HDAC）的蛋白质表达。这些发现表明CRA在TRAMP-C1细胞中具有显著的抗癌作用，这可能部分归因于表观遗传学，包括其表观遗传学恢复Nrf 2表达的能力。
Corosolic acid (CRA) is found in various plants and has been used as a health food supplement worldwide. Although it has been reported that CRA exhibits significant anticancer activity, the effect of this compound on prostate cancer remains unknown. In this study, we investigated the effect of CRA on cellular transformation and the reactivation of nuclear factor erythroid 2-related factor 2 (Nrf2) through epigenetic regulation in TRAMP-C1 prostate cells. Specifically, we found that CRA inhibited anchorage-independent growth of prostate cancer TRAMP-C1 cells but not Nrf2 knockout prostate cancer TRAMP-C1 cells. Moreover, CRA induced mRNA and protein expression of Nrf2, heme oxygenase-1 (HO-1) and quinone oxidoreductase-1 (NQO1). Bisulfate genomic sequencing and methylated DNA immunoprecipitation results revealed that CRA treatment decreased the level of methylation of the first five CpG sites of the Nrf2 promoter. Histone modification was analyzed using a chromatin immunoprecipitation (ChIP) assay, which revealed that CRA treatment increased the acetylation of histone H3 lysine 27 (H3K27ac) while decreasing the trimethylation of histone H3 lysine 27 (H3K27me3) in the promoter region of Nrf2. Furthermore, CRA treatment attenuated the protein expression of DNA methyltransferases (DNMTs) and histone deacetylases (HDACs). These findings indicate that CRA has a significant anticancer effect in TRAMP-C1 cells, which could be partly attributed to epigenetics including its ability to epigenetically restore the expression of Nrf2.
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影响因子：
3.8
作者：
Ngollo M;Lebert A;Daures M;Judes G;Rifai K;Dubois L;Kemeny JL;Penault-Llorca F;Bignon YJ;Guy L;Bernard-Gallon D
通讯作者：
Bernard-Gallon D
影响因子：
7.5
作者：
Saw CL;Yang AY;Huang MT;Liu Y;Lee JH;Khor TO;Su ZY;Shu L;Lu Y;Conney AH;Kong AN
通讯作者：
Kong AN
影响因子：
5.6
作者：
Baumgart SJ;Haendler B
通讯作者：
Haendler B
影响因子：
3.3
作者：
Chen, Hong;Yang, Jie;Wang, Qiang
通讯作者：
Wang, Qiang
委陵菜治疗2型糖尿病的代谢组学分析
影响因子：
--
作者：
Li, Yi;Li, Jing-jing;Yang, Jie
通讯作者：
Yang, Jie