The Small Glutathione Peroxidase Mimic 5P May Represent a New Strategy for the Treatment of Liver Cancer

Abstract

Glutathione peroxidase (GPx) is an antioxidant protein containing selenium. Owing to the limitations of native GPx, considerable efforts have been made to develop GPx mimics. Here, a short 5-mer peptides (5P) was synthesized and characterized using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Enzyme coupled assays were used to evaluate GPx activity. The cell viability and apoptosis of H22 cells were tested, and mice bearing H22 cell-derived tumors were used to determine the effects of 5P on tumor inhibition. In comparison with other enzyme models, 5P provided a suitable substrate with proper catalytic site positions, resulting in enhanced catalytic activity. In our mouse model, 5P showed excellent inhibition of tumor growth and improved immunity. In summary, our findings demonstrated the design and synthesis of the small 5P molecule, which inhibited tumor growth and improved immunity. Notably, 5P could inhibit tumor growth without affecting normal growth. Based on these advantages, the novel mimic may have several clinical applications.

Peptide-Based Drugs and Drug Delivery Systems

“…Glutathione peroxidase (GPx) is an important antioxidant enzyme and considerable efforts have been made to develop GPx mimics. Yin et al [ 27 ] reported on the design and activity of short 5-mer peptides (5P) effective in the treatment of liver cancer in vitro and in vivo. In summary, they showed that 5P could overcome many of the limitations of traditional anticancer drugs, and could be used at low doses to inhibit tumor growth.…”

Targeting the Antioxidant Enzymes for the Treatment of Reactive Oxygen Species (ROS)-Induced Cancer

“…GPx3 is reported to suppress a tumor progression (Chang et al 2020). A short 5 amino acid [5 mer peptide Arg-Gly-Ser-Arg-Asn] peptide synthesized to mimic GPx represents a good strategy to treat hepatocellular carcinoma (Yin et al 2017). Silencing of GPx2 gene using Si-RNA prevented epithelial-mesenchymal transition through reduced Wnt signaling in pancreatic cancer (Li et al 2020).…”