Hoda Muddasarul, Pajaniradje Sankar, Shakya Garima, Mohankumar Kumaravel, Rajagopalan Rukkumani
Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Puducherry, India.
Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Puducherry, India; Interdisciplinary Programme for Life Sciences, Pondicherry University, Puducherry, India; Department of Biotechnology, University of Madras, Guindy Campus, Chennai, Tamilnadu, India.
Nanomedicine. 2016 Aug;12(6):1641-50. doi: 10.1016/j.nano.2016.02.013. Epub 2016 Mar 22.
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.
重新研究已知药物的抗癌潜力正成为一种新趋势。一种具有显著抗癌潜力的抗酒精药物双硫仑，被用于研究其对肝癌体外模型Hep3B细胞系的疗效。同时，我们打算研究聚山梨酯80稳定的聚乳酸-羟基乙酸共聚物（PLGA）纳米颗粒及其负载双硫仑的对应物的效果。进行了细胞和细胞核染色、彗星试验、流式细胞术和蛋白质免疫印迹分析。结果表明，双硫仑及其PLGA纳米颗粒通过细胞周期阻滞抑制细胞增殖，触发凋亡途径的激活，最终导致细胞死亡。与游离双硫仑相比，负载双硫仑的纳米颗粒由于其持续释药特性，效果显著降低，而空纳米颗粒对Hep3B细胞的影响可忽略不计。我们的结果表明，单独使用双硫仑会导致细胞死亡，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，这可能会降低给药方案。
