Inhibitory effect of Erinacines A on the growth of DLD-1 colorectal cancer cells is induced by generation of reactive oxygen species and activation of p70S6K and p21
Inhibitory effect of Erinacines A on the growth of DLD-1 colorectal cancer cells is induced by generation of reactive oxygen species and activation of p70S6K and p21
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DOI：
10.1016/j.jff.2015.12.031
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发表时间：
2016-03-01
影响因子：
5.6
通讯作者：
Kuo, Hsing-Chun
中科院分区：
文献类型：
--
作者：
Lu, Chien-Chang;Huang, Wen-Shih;Kuo, Hsing-Chun
猴头菌（Hericium erinaceus）是一种著名的食用菌，具有重要的生物学特性。Erinacine A是该菌菌丝体中二萜类化合物的主要活性成分。刺猬。该药剂具有多种生理活性，包括抗肿瘤活性。在这项研究中，我们研究了erinacine A介导活性氧（ROS）产生的分子机制，并进行了细胞周期阻滞，以澄清结直肠癌细胞（CRC）的分子变化。用erinacine A处理DLD-1细胞导致c-Jun N-末端激酶（JNK）和p70 S6 K的磷酸化，p50和p-IKB-β蛋白水平的活化，细胞周期相关蛋白（细胞周期蛋白A、cdk 2、细胞周期蛋白E、cdk 4和细胞周期蛋白D1）的下调，以及p21的诱导。此外，用N-乙酰半胱氨酸（NAC）和mTOR抑制剂（雷帕霉素）处理废除了erinacine A诱导的细胞周期G1停滞，并逆转了CDK 2与细胞周期蛋白E和CDK 4与细胞周期蛋白D1的关联。因此，当DLD-1细胞在裸鼠中作为异种移植物生长时，用erinacine A处理诱导肿瘤生长的显著剂量依赖性降低。组织化学和免疫组化分析表明，erinacine A治疗显着减少有丝分裂细胞的数量。这些结果表明，erinacine
Hericium erinaceus is a well-known edible mushroom with valuable biological properties. Erinacine A is the major active agent of the diterpenoid compounds of the cultured mycelia of H. erinaceus. This agent has multiple physiological activities, including anti-tumourigenic activity. In this study, we investigated the molecular mechanisms by which erinacine A mediated the generation of reactive oxygen species (ROS), and we performed cell cycle arrest to clarify molecular changes in colorectal cancer cells (CRC). Treatment of DLD-1 cells with erinacine A resulted in the phosphorylation of c-Jun N-terminal kinase (JNK) and p70S6K, the activation of p50 and p-IKB-beta protein levels, the downregulation of cell-cycle-related proteins (cyclin A, cdk2, cyclin E, cdk4, and cyclin D1), and the induction of p21. Furthermore, treatment with the N-acetyl cysteine (NAC) and mTOR inhibitor (rapamycin) abolished erinacine A-induced cell cycle G1 arrest and reversed the association of CDK2 with Cyclin E and CDK4 with Cyclin D1. Therefore, when DLD-1 cells were grown as xenografts in nude mice, treatment with erinacine A induced a significant dose-dependent decrease in tumour growth. Histochemical and immunohistochemical analysis revealed that erinacine A treatment significantly reduced the number of mitotic cells. These results suggest that erinacine