Anti-proliferative and apoptosis-triggering potential of disulfiram and disulfiram-loaded polysorbate 80-stabilized PLGA nanoparticles on hepatocellular carcinoma Hep3B cell line
Anti-proliferative and apoptosis-triggering potential of disulfiram and disulfiram-loaded polysorbate 80-stabilized PLGA nanoparticles on hepatocellular carcinoma Hep3B cell line
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DOI：
10.1016/j.nano.2016.02.013
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发表时间：
2016-08-01
影响因子：
5.4
通讯作者：
Rajagopalan, Rukkumani
中科院分区：
文献类型：
--
作者：
Hoda, Muddasarul;Pajaniradje, Sankar;Rajagopalan, Rukkumani
重新研究已知药物的抗癌潜力已成为一种新兴趋势。人们研究了一种具有显着抗癌潜力的抗酒精药物双硫仑对 Hep3B 细胞系（一种肝细胞癌的体外模型）的功效。同时，我们打算研究聚山梨酯 80 稳定的 PLGA 纳米颗粒及其 DSF 负载对应物的效果。进行了细胞和核染色、彗星测定、流式细胞术和蛋白质印迹。结果表明，DSF 及其 PLGA 纳米粒子通过细胞周期停滞抑制细胞增殖，触发细胞凋亡途径的激活，最终导致细胞死亡。与游离 DSF 相比，负载 DSF 的纳米颗粒由于其持续的药物释放特性而表现出明显较小的效果，而空纳米颗粒对 Hep3B 细胞的影响可以忽略不计。我们的结果表明，DSF 单独导致细胞死亡，而聚山梨酯 80 稳定的 PLGA 纳米颗粒显示出持续的药物释放模式，可能会降低剂量方案。 (C) 2016 Elsevier Inc. 保留所有权利。
There is an emerging trend to restudy known drugs for their anti-cancer potential. One such anti-alcoholic drug, disulfiram, with significant anti-cancer potential was studied for its efficacy against Hep3B cell lines, an in vitro model of hepatocellular carcinoma. Simultaneously, we intended to study the effect of polysorbate 80-stabilized PLGA nanoparticles and its DSF-loaded counterpart. Cell and nuclear staining, comet assay, flow cytometry and Western blots were performed. Results suggest that cell proliferation was inhibited by DSF and its PLGA nanoparticles through cell cycle arrest, triggering activation of apoptotic pathways that culminates with cell death. DSF loaded nanoparticles when compared with free DSF, showed significantly lesser effect due to its sustained drug-releasing property, while empty nanoparticles showed negligible influence on Hep3B cells. Our results suggest that DSF alone contributes to cell death, while polysorbate 80-stabilized PLGA nanoparticles show sustained drug release patterns that would potentially lower dosage regimens. (C) 2016 Elsevier Inc. All rights reserved.