Kumari Manisha, Ray L, Purohit M P, Patnaik S, Pant A B, Shukla Y, Kumar P, Gupta K C
CSIR-Institute of Genomics and Integrative Biology, Delhi University Campus, Mall Road, Delhi 110007, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India.
CSIR-Indian Institute of Toxicology Research, M.G. Marg, Lucknow 226 001, Uttar Pradesh, India.
Eur J Pharm Biopharm. 2017 Aug;117:346-362. doi: 10.1016/j.ejpb.2017.05.003. Epub 2017 May 9.
The anticancer properties of selenium (Se) and curcumin nanoparticles in solo formulations as well as in combination with other therapeutic agents have been proved time and again. Exploiting this facet of the two, we clubbed their tumoricidal characteristics and designed curcumin loaded Se nanoparticles (Se-CurNPs) to achieve an enhanced therapeutic effect. We evaluated their therapeutic effects on different cancer cell lines and Ehrlich's ascites carcinoma mouse model. In vitro results showed that Se-CurNPs were most effective on colorectal carcinoma cells (HCT116) compared to the other cancer cell lines used and possessed pleiotropic anticancer effects. The therapeutic effect on HCT116 was primarily attributed to an elevated level of autophagy and apoptosis as evident from significant up-regulation of autophagy associated (LC3B-II) and pro-apoptotic (Bax) proteins, down-regulation of anti-apoptotic (Bcl-2) protein and Cytochrome c (cyt c) release from mitochondria along with reduced NFκB signaling and EMT based machineries marked by downregulation of inflammation (NFκB, phospho-NFκB) and epithelial-mesenchymal transition (CD44, N-cadherin) associated proteins. In vivo studies on Ehrlich's ascites carcinoma (EAC) mice model indicated that Se-CurNPs significantly reduced the tumor load and enhanced the mean survival time (days) of tumor-bearing EAC mice.
单独制剂以及与其他治疗剂联合使用时,硒(Se)和姜黄素纳米颗粒的抗癌特性已被反复证明。利用这两种物质的这一方面,我们将它们的杀肿瘤特性结合起来,设计了负载姜黄素的硒纳米颗粒(Se-CurNPs)以实现增强的治疗效果。我们评估了它们对不同癌细胞系和艾氏腹水癌小鼠模型的治疗效果。体外结果表明,与所使用的其他癌细胞系相比,Se-CurNPs对结肠癌细胞(HCT116)最有效,并具有多效抗癌作用。对HCT116的治疗效果主要归因于自噬和凋亡水平的升高,这从自噬相关蛋白(LC3B-II)和促凋亡蛋白(Bax)的显著上调、抗凋亡蛋白(Bcl-2)的下调、细胞色素c(cyt c)从线粒体的释放以及炎症(NFκB、磷酸化-NFκB)和上皮-间质转化(CD44、N-钙黏蛋白)相关蛋白下调所标记的NFκB信号和EMT相关机制的减少中可以明显看出。对艾氏腹水癌(EAC)小鼠模型的体内研究表明,Se-CurNPs显著降低了肿瘤负荷,并延长了荷瘤EAC小鼠的平均存活时间(天)。