Litchi seed extracts diminish prostate cancer progression via induction of apoptosis and attenuation of EMT through Akt/GSK-3β signaling.
Litchi seed extracts diminish prostate cancer progression via induction of apoptosis and attenuation of EMT through Akt/GSK-3β signaling.
复制标题
荔枝籽提取物通过 Akt/GSK-3 beta 信号传导诱导细胞凋亡和减弱 EMT，从而减少前列腺癌的进展
DOI：
10.1038/srep41656
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发表时间：
2017-01-30
影响因子：
4.6
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Guo H;Luo H;Yuan H;Xia Y;Shu P;Huang X;Lu Y;Liu X;Keller ET;Sun D;Deng J;Zhang J
荔枝（Litchi chinensisSonnnerat，无患子科）又名中国樱桃，是原产于我国南方的亚热带果树。荔枝核提取物具有多种药理作用，包括抗癌作用。然而，其对前列腺癌的抗癌作用和机制尚未确定。在这项研究中，我们使用荔枝核正丁醇提取物（NLS）治疗前列腺癌PC 3、DU 145、RM 1和C4-2B细胞。NLS以剂量依赖性方式诱导细胞活力和克隆形成生长显著降低。NLS通过抑制Akt信号通路，诱导细胞凋亡，使细胞周期阻滞于G1/S期，这与激活线粒体caspase依赖的凋亡级联反应，上调细胞周期蛋白依赖性激酶（cyclin-dependent kinase，CDK）抑制剂p21和p27的表达，抑制相关的cyclin/CDK网络有关。另外，NLS通过逆转EMT表型，显著降低细胞的迁移和侵袭能力，并与E-cadherin和β-catenin表达增加，vimentin和snail表达降低相关，这可能与抑制Akt/GSK-3β信号通路有关。最后，在体内用NLS处理的PC 3异种移植裸鼠显示出肿瘤大小的显著减小而没有毒性。这些发现表明，NLS有潜力发展成为前列腺癌患者安全有效的替代疗法。
Litchi (Litchi chinensisSonnnerat, Sapindaceae), known as Chinese Cherry, is a subtropical fruit tree originating from southern China. Litchi seed extracts have diverse pharmacological effects, including anticancer. However, its anticancer effects and mechanisms on prostate cancer have not been determined. In this study, we used n-butyl alcohol extract of Litchi seed (NLS) to treat prostate cancer PC3, DU145, RM1 and C4-2B cells. NLS induced a significant decrease in cell viability and clonogenic growth in a dose-dependent manner. NLS induced cell apoptosis and cell cycle G1/S phase arrest by inactivating Akt signaling pathway, which were associated with activation of mitochondrial caspase-dependent apoptotic cascades, up-regulation of cyclin-dependent kinase (CDK) inhibitors p21 and p27, and inhibition of correlated cyclin/CDK network. In addition, NLS treatment significantly decreased cell migration and invasion via phenotypic inversion of EMT, correlated with increased expression of E-cadherin and β-catenin, and decreased expression of vimentin and snail, which is partially attributed to inhibiting Akt/GSK-3β signaling pathway. Finally, PC3 xenograft nude mice treated with NLS in vivo showed a significant decrease in tumor size without toxicity. These findings suggest that NLS has potential for development into a safe and potent alternative therapy for prostate cancer patients.