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

Overview

Journal ACS Omega

Publisher American Chemical Society

Specialty Chemistry

Date 2020 May 12

PMID 32391458

Citations 34

Authors

Aparna Datta

Snehasis Mishra

Krishnendu Manna

Krishna Das Saha

Siddhartha Mukherjee

Somenath Roy

Affiliations

Soon will be listed here.

Abstract

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 (CeO) 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, CeO would function as a pro-oxidant. Based on this concept, the present study is designed to investigate the pro-oxidant activities of CeO 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 CeO nanoparticles of different concentrations (5-100 μg/mL) in the culture media. The half maximal inhibitory concentration (IC) of nanoceria for HCT 116 is found to be 50.48 μg/mL while that for the HEK 293 cell line is 92.03 μg/mL. To understand the intricate molecular mechanisms of CeO-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 release, intracellular ROS analysis, and mitochondrial membrane potential analysis using flow cytometry. Experimental data suggest that CeO treatment causes DNA fragmentation through enhanced generation of ROS, which ultimately leads to cellular apoptosis through the p53-dependent mitochondrial signaling pathway.

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