Pro-Oxidant Therapeutic Activities of Cerium Oxide Nanoparticles in Colorectal Carcinoma Cells

被引:87
作者
Datta, Aparna [1 ]
Mishra, Snehasis [2 ]
Manna, Krishnendu [2 ]
Das Saha, Krishna [2 ]
Mukherjee, Siddhartha [3 ]
Roy, Somenath [4 ]
机构
[1] Jadavpur Univ, Sch Mat Sci & Nanotechnol, Kolkata 700032, W Bengal, India
[2] CSIR Indian Inst Chem Biol, Canc Biol & Inflammatory Disorder Div, Kolkata 700032, W Bengal, India
[3] Jadavpur Univ, Dept Met & Mat Engn, Kolkata 700032, W Bengal, India
[4] CSIR Cent Glass & Ceram Res Inst, Kolkata 700032, W Bengal, India
关键词
CANCER; ACTIVATION; MECHANISMS; APOPTOSIS; ROS;
D O I
10.1021/acsomega.9b04006
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Given that basal levels of reactive oxygen species (ROS) are higher in cancer cells, there is a growing school of thought that endorses pro-oxidants as potential chemotherapeutic agents. Intriguingly, cerium oxide (CeO2) nanoparticles can manifest either anti- or pro-oxidant activity as a function of differential pH of various subcellular localizations. In an acidic pH environment, for example, in extracellular milieu of cancer cells, CeO2 would function as a pro-oxidant. Based on this concept, the present study is designed to investigate the pro-oxidant activities of CeO2 in human colorectal carcinoma cell line (HCT 116). For comparison, we have also studied the effect of ceria nanoparticles on human embryonic kidney (HEK 293) cells. Dose-dependent viability of cancerous as well as normal cells has been assessed by treating them independently with CeO2 nanoparticles of different concentrations (5-100 mu g/mL) in the culture media. The half maximal inhibitory concentration (IC50) of nanoceria for HCT 116 is found to be 50.48 mu g/mL while that for the HEK 293 cell line is 92.03 mu g/mL. To understand the intricate molecular mechanisms of CeO2-induced cellular apoptosis, a series of experiments have been conducted. The apoptosis-inducing ability of nanoceria has been investigated by Annexin V-FITC staining, caspase 3/9 analysis, cytochrome c release, intracellular ROS analysis, and mitochondrial membrane potential analysis using flow cytometry. Experimental data suggest that CeO2 treatment causes DNA fragmentation through enhanced generation of ROS, which ultimately leads to cellular apoptosis through the p53-dependent mitochondrial signaling pathway.
引用
收藏
页码:9714 / 9723
页数:10
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