Exposure to cadmium and copper triggers cytotoxic effects and epigenetic changes in human colorectal carcinoma HT‑29 cells
Andrada Iftode, George Andrei Drăghici, Ioana Macașoi, Iasmina Marcovici, Dorina Coricovac, Răzvan Drăgoi, Alina Andreea Tischer, Leda Kovatsi, Aristidis Tsatsakis, Octavian Creţu, Cristina Dehelean
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 CdCl<sub>2</sub> and CuSO<sub>4</sub> 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 <em>µ</em>g/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.