Impact assessment of cadmium chloride on human cell lines and yeast knockout strains

Abstract

Background Cadmium (Cd) is a heavy metal that contributes to pollution in the environment. Cd intoxication can lead to diseases in the liver, kidneys, and lungs, among other organs. The liver is the primary organ affected by Cd overdose.Objective To evaluate the cytotoxic and genotoxic responses of cadmium chloride (CdCl2) on three different human cell lines and four different genotypes of yeast knockout strains.Materials and methods The effects of different concentrations of CdCl2 on cell viability in hepatocellular carcinoma (HepG2), lung cancer (A549), and normal lung cell carcinoma (Wi38) were investigated systematically using the MTT method. Moreover, flow cytometry was used to assess cell cycle arrest using propidium iodide (PI) staining and to quantify apoptotic cell death using PI staining and Annexin V/PI staining, respectively. The gene expression of p53, casp3, and Bcl-2 was measured using qRT-PCR. The Comet methodology was used to indicate DNA damage of yeast knockout strains.Results and conclusion The MTT assay revealed that CdCl2 was highly potent against hepatocellular carcinoma (HepG2), lung cancer (A549), and normal lung cell lines (Wi38) (IC50=3.12, 28.81, 191.14 μg/ml). These findings showed that CdCl2 reduced therapeutic efficacy in malignant cells at relatively low concentrations compared with nonmalignant cells, as well as confirmed the antitumor effect of the metal. CdCl2-damaged A549 cells revealed a significant increase in arrest of cell cycle in ‘S’ phases, and then apoptosis increased. Subsequently, when A549 cells were treated with a higher dosage of CdCl2, the gene expression of p53 and casp3 genes was upregulated, whereas Bcl-2 was downregulated. CdCl2 revealed its genotoxic activity at different concentrations of 10, 25, 50 μg/ml. MRE11, CLN1 and ZRC1 genes exhibited marked genotoxic effects, while MMT1 gene generated modret genotoxicity of yeast knockout strains. The Comet assay revealed that yeast cells were more responsive, which was indisputably demonstrated.