The Anti-Tumor Effect of Zinc on Renal Cell Carcinoma by Enhancing Autophagy

Abstract

Renal cell carcinoma remains one of the most common malignant tumorsand is associated with significant challenges in drug therapy. Zinc has been reported to be of pharmacological importance and immense potential in the inhibition of renal cell carcinoma cells. In order to investigate the inhibitory effect of zinc on the human renal cell carcinoma cell line A498, its anti-proliferative activity was investigated using the CCK8 assay. The oxidative stress status and mitochondrial injury were detected by DCFH-DA and JC-1 staining, respectively. The expression of autophagy-related proteins was determined by western blot analysis, which aimed at exploring the antioxidant mechanisms of zinc. Over 40% yield of ROS and more than four times the number of autophagosomes were detected in the experimental group treated by zinc compared to the control group. Furthermore, zinc led to up-regulation of the Beclin 1-related signaling pathway in the late stage of autophagy degradation. Zinc demonstrated a good inhibitory effect on A498 cells with the value of IC50similar to the values of natural products. One of the mechanisms of zinc is enhancing the Beclin 1-dependent autophagy. Taken together, with its low cost and natural properties, zinc could become a promising molecule with satisfied anti-tumor effect and low cost in the treatment of renal cell carcinoma.