Oral administration of naturally occurring chitosan-based nanoformulated green tea polyphenol EGCG effectively inhibits prostate cancer cell growth in a xenograft model
Oral administration of naturally occurring chitosan-based nanoformulated green tea polyphenol EGCG effectively inhibits prostate cancer cell growth in a xenograft model
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DOI：
10.1093/carcin/bgt321
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发表时间：
2014-02-01
期刊：
影响因子：
4.7
通讯作者：
Mukhtar, Hasan
中科院分区：
文献类型：
--
作者：
Khan, Naghma;Bharali, Dhruba J.;Mukhtar, Hasan
在临床前动物模型中，几种植物化学物质已显示出极好的潜力，可用作预防和治疗许多癌症的有效药物。然而，活性剂有限的生物利用度可能是其对人类消费的有用性受限的一个原因。为了克服这一限制，我们最近引入了纳米化学预防的概念，通过封装有用的生物活性食品成分，使其缓慢和持续释放。在这里，我们报告的合成，表征和疗效评估的纳米技术为基础的口服制剂的壳聚糖纳米颗粒封装表没食子儿茶素-3-没食子酸酯（Chit-nanoEGCG）的前列腺癌（PCa）的治疗在临床前设置。动态光散射和透射电镜结果表明，粒径小于200 nm的壳聚糖纳米EGCG包封物在模拟胃液中释放缓慢，在模拟肠液中释放较快。在皮下植入22 R？1无胸腺裸鼠移植瘤。与EGCG和对照组相比，用Chit-nanoEGCG治疗导致肿瘤生长和分泌的前列腺特异性抗原水平的显著抑制。在用Chit-nanoEGCG处理的小鼠的肿瘤组织中，与用EGCG处理的组和对照组相比，存在显著的（i）多聚（ADP-核糖）聚合酶切割的诱导，（ii）Bax蛋白表达的增加伴随Bcl-2的减少，（iii）半胱天冬酶的活化和（iv）Ki-67和增殖细胞核抗原的减少。通过这项研究，我们提出了一种新的预防和治疗模式，PCa使用表没食子儿茶素没食子酸酯，解决了生物利用度相关的问题。
In preclinical animal models, several phytochemicals have shown excellent potential to be used as effective agents in preventing and treating many cancers. However, the limited bioavailability of active agents could be one reason for their restricted usefulness for human consumption. To overcome this limitation, we recently introduced the concept of nanochemoprevention by encapsulating useful bioactive food components for their slow and sustained release. Here, we report the synthesis, characterization and efficacy assessment of a nanotechnology-based oral formulation of chitosan nanoparticles encapsulating epigallocatechin-3-gallate (Chit-nanoEGCG) for the treatment of prostate cancer (PCa) in a preclinical setting. Chit-nanoEGCG with a size of < 200nm diameter and encapsulating EGCG as determined by dynamic light scattering and transmission electron microscope showed slow release of EGCG in simulated gastric juice acidic pH and faster release in simulated intestinal fluid. The antitumor efficacy of Chit-nanoEGCG was assessed in subcutaneously implanted 22R?1 tumor xenografts in athymic nude mice. Treatment with Chit-nanoEGCG resulted in significant inhibition of tumor growth and secreted prostate-specific antigen levels compared with EGCG and control groups. In tumor tissues of mice treated with Chit-nanoEGCG, compared with groups treated with EGCG and controls, there was significant (i) induction of poly (ADP-ribose) polymerases cleavage, (ii) increase in the protein expression of Bax with concomitant decrease in Bcl-2, (iii) activation of caspases and (iv) reduction in Ki-67 and proliferating cell nuclear antigen. Through this study, we propose a novel preventive and therapeutic modality for PCa using EGCG that addresses issues related to bioavailability.