Experimental and therapeutic medicine · 2020
Exposure to cadmium and copper triggers cytotoxic effects and epigenetic changes in human colorectal carcinoma HT-29 cells.
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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
Аннотация
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.