Abstract
Cerium oxide nanocrystals (CeO2-NCs) exhibit superoxide dismutase and catalase mimetic activities. Based on these catalytic activities, CeO2-NCs have been suggested to have the potential to treat various diseases. The crystalline size of these materials is an important factor that influences the performance of CeO2-NCs. Previous reports have shown that several metal-based nanocrystals, including CeO2-NCs, can induce cytotoxicity in cancer cells. However, the underlying mechanisms have remained unclear. To characterize the anticancer activities of CeO2-NCs, several assays related to the mechanism of cytotoxicity and induction of apoptosis has been performed. Here, we have carried out a systematic study to characterize CeO2-NCs phase purity (X-ray diffraction), morphology (electron microscopy), and optical features (optical absorption, Raman scattering, and photoluminescence) to better establish their potential as anticancer drugs. Our study revealed anticancer effects of CeO2-NCs in HT29 and SW620 colorectal cancer cell lines with half-maximal inhibitory concentration (IC50) values of 2.26 and 121.18 μg ml–1, respectively. Reductions in cell viability indicated the cytotoxic potential of CeO2-NCs in HT29 cells based on inverted and florescence microscopy assessments. The mechanism of cytotoxicity confirmed by estimating possible changes in the expression levels of Bcl2, BclxL, Bax, PARP, cytochrome c, and β-actin (control) proteins in HT29 cells. Down-regulation of Bcl2 and BclxL and up-regulation of Bax, PARP, and cytochrome c proteins suggested the significant involvement of CeO2-NCs exposure in the induction of apoptosis. Furthermore, biocompatibility assay showed minimum effect of CeO2-NCs on human red blood cells.
Highlights
Nanobiotechnology, a rapidly emerging field of advanced materials science, has expanded the possibility for advances in medical sciences such as gene-delivery systems, targeted drug delivery, and artificial implants [1,2,3]
We used an aqueous environment to prepare CeO2-NCs, which has large amount of hydroxyl groups on the surface of nanocrystals. Because of these surface hydroxyl groups, CeO2-NCs are biocompatible and less toxic. They may be considered to be eco-friendly and do not pose significant environmental hazards, in contrast to those compounds used for the chemical reduction method [37]
The cytotoxic effects of CeO2-NCs on colon cancer cell lines suggest that CeO2-NCs can play an important role in the development of drugs against colorectal cancer
Summary
CeO2-NCs act as potential therapeutic agents against various diseases, including cancer, with the least toxicity towards normal cells and tissues [15,16]. CeO2-NCs exhibit antioxidant properties that may counteract the progression of various diseases, including cancer, that are associated with oxygen levels and ROS generation [22]. Several studies that assessed the activity of CeO2NCs in cancer showed that CeO2-NCs have anti-invasive effects against several types of cancer cells [23], and confer radioprotection to normal cells and induce radio-sensitization [24] by controlling the extent of ROS and antioxidant enzyme activities [25]. We observed that exposure of CeO2-NCs to the HT29 cancer cell line altered the normal expression levels of Bcl, BclxL, Bax, PARP, and cytochrome c proteins
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