Exposure to cadmium and copper triggers cytotoxic effects and epigenetic changes in human colorectal carcinoma HT‑29 cells

Iftode,Andrada; Drăghici,George Andrei; Macașoi,Ioana; Marcovici,Iasmina; Coricovac,Dorina E.; Dragoi,Razvan; Tischer,Alina; Kovatsi,Leda; Tsatsakis,Aristidis M.; Cretu,Octavian; Dehelean,Cristina

doi:10.3892/etm.2020.9532

Exposure to cadmium and copper triggers cytotoxic effects and epigenetic changes in human colorectal carcinoma HT‑29 cells

Authors:
- Andrada Iftode
- George Andrei Drăghici
- Ioana Macașoi
- Iasmina Marcovici
- Dorina E. Coricovac
- Razvan Dragoi
- Alina Tischer
- Leda Kovatsi
- Aristidis M. Tsatsakis
- Octavian Cretu
- Cristina Dehelean
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Affiliations: Department of Toxicology and Drug Industry, Faculty of Pharmacy, ‘Victor Babes’ University of Medicine and Pharmacy, 300041 Timisoara, Romania, Department of Balneology, Rehabilitation and Rheumatology, ‘Victor Babes’ University of Medicine and Pharmacy, 300041 Timisoara, Romania, Department of Surgery I, Faculty of Medicine, ‘Victor Babes’ University of Medicine and Pharmacy, 300041 Timisoara, Romania, Laboratory of Forensic Medicine and Toxicology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece, Department of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, 71003 Heraklion, Greece
Published online on: November 26, 2020 https://doi.org/10.3892/etm.2020.9532
Article Number: 100
Copyright: © Iftode et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Recent scientific evidence suggests a link between epigenetic changes (DNA methylation) and tumorigenesis. Moreover, a potential carcinogenic mechanism of cadmium was associated with changes in DNA methylation. In this study we investigated the impact of CdCl₂ and CuSO₄ aqueous solutions on DNA methylation in HT‑29 cells by quantifying DNA methyltransferase (DNMT1, DNMT3A and DNMT3B) mRNA expression. Furthermore, we also studied the cytotoxic and anti‑migratory potential of these substances. The results showed a dose‑dependent decrease of viable cell percentage following 24 h of exposure (at concentrations of 0.05; 0.2; 1; 10 and 100 µg/ml), and an inhibitory effect on HT‑29 cell migration capacity. In addition, RT‑qPCR results showed that cadmium acts as a hypomethylating agent by suppressing DNMT expression, whereas copper acts as a hypermethylating compound by increasing DNMT expression. These findings suggest a cytotoxic potential of both cadmium and copper on HT‑29 cells and their capacity to induce epigenetic changes.

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