Gold-chrysophanol nanoparticles suppress human prostate cancer progression through inactivating AKT expression and inducing apoptosis and ROS generation in vitro and in vivo.
Gold-chrysophanol nanoparticles suppress human prostate cancer progression through inactivating AKT expression and inducing apoptosis and ROS generation in vitro and in vivo.
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DOI：
10.3892/ijo.2017.4095
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发表时间：
2017-10
影响因子：
5.2
通讯作者：
Wang ZY
中科院分区：
文献类型：
--
作者：
Lu L;Li K;Mao YH;Qu H;Yao B;Zhong WW;Ma B;Wang ZY
控释制剂仍然是递送各种药物的最方便的方法。在本研究中，我们用大黄酚沉淀金纳米颗粒。将金大黄酚负载到聚（DL-丙交酯-乙交酯）纳米粒中，并测试大黄酚纳米粒对人前列腺癌LNCap细胞的生物活性，以获得缓释性能。圆二色谱分析表明，大黄酚纳米粒有效地导致DNA的构象变化，并调节与细胞周期阻滞相关的不同蛋白质。检测细胞活性氧（ROS）、细胞凋亡、细胞周期、DNA损伤、Cyto-c和caspase-3活性，并采用免疫印迹法检测不同抗凋亡和促凋亡基因的表达水平。细胞毒性试验表明，与正常细胞相比，大黄酚纳米颗粒优先杀死前列腺癌细胞。胆固醇纳米颗粒通过减少组蛋白脱乙酰酶（HDAC）来抑制细胞增殖并通过将细胞周期阻滞在亚G期来诱导凋亡。此外，大黄酚纳米粒还可调控细胞周期相关蛋白，包括p27、CHK 1、cyclin D1、CDK 1、p-AMP-activated protein kinase（AMPK）和p-蛋白激酶B（AKT），从而阻止人前列腺癌细胞的进展。胆甾醇纳米颗粒通过促进p53/ROS串扰来诱导LNCap细胞凋亡以防止增殖。在小鼠体内的药代动力学研究表明，与游离大黄酚相比，大黄酚纳米粒注射液显示出更高的生物利用度。体内实验表明，大黄酚纳米粒可明显缩小肿瘤体积和重量。综上所述，上述数据表明大黄酚纳米颗粒可能有效预防人类前列腺癌进展。
Controlled releasing of regulations remains the most convenient method to deliver various drugs. In the present study, we precipitated gold nanoparticles with chrysophanol. The gold-chrysophanol into poly (DL-lactide-co-glycolide) nanoparticles was loaded and the biological activity of chrysophanol nanoparticles on human LNCap prostate cancer cells, was tested to acquire the sustained releasing property. The circular dichroism spectroscopy indicated that chrysophanol nanoparticles effectively resulted in conformational alterations in DNA and regulated different proteins associated with cell cycle arrest. The reactive oxygen species (ROS), apoptosis, cell cycle, DNA damage, Cyto-c and caspase-3 activity were analyzed, and the expression levels of different anti- and pro-apoptotic were studied using immunoblotting analysis. The cytotoxicity assay suggested that chrysophanol nanoparticles preferentially killed prostate cancer cells in comparison to the normal cells. Chrysophanol nanoparticles reduced histone deacetylases (HDACs) to suppress cell proliferation and induce apoptosis by arresting the cell cycle in sub-G phase. In addition, the cell cycle-related proteins, including p27, CHK1, cyclin D1, CDK1, p-AMP-activated protein kinase (AMPK) and p-protein kinase B (AKT), were regulated by chrysophanol nanoparticles to prevent human prostate cancer cell progression. Chrysophanol nanoparticles induced apoptosis in LNCap cells by promoting p53/ROS crosstalk to prevent proliferation. Pharmacokinetic study in mice indicated that chrysophanol nanoparticle injection showed high bioavailability compared to the free chrysophanol. Also, in vivo study revealed that chrysophanol nanoparticles obviously reduced tumor volume and weight. In conclusion, the data above suggested that chrysophanol nanoparticles might be effective to prevent human prostate cancer progression.
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影响因子：
--
作者：
Aldana-Masangkay GI;Sakamoto KM
通讯作者：
Sakamoto KM
影响因子：
56.9
作者：
Choudhary, Chunaram;Kumar, Chanchal;Mann, Matthias
通讯作者：
Mann, Matthias
影响因子：
64.8
作者：
Hubbert, C;Guardiola, A;Yao, TP
通讯作者：
Yao, TP
影响因子：
10.8
作者：
Lin, Ts-Ting;Gao, Dong-Yu;Chen, Yunching
通讯作者：
Chen, Yunching
影响因子：
64.5
作者：
Gu, W;Roeder, RG
通讯作者：
Roeder, RG