Metal Complex Formation and Anticancer Activity of Cu(I) and Cu(II) Complexes with Metformin

Metformin has been used for decades in millions of type 2 diabetes mellitus patients. In this time, correlations between metformin use and the occurrence of other disorders have been noted, as well as unpredictable metformin side effects. Diabetes is a significant cancer risk factor, but unexpectedly, metformin-treated diabetic patients have lower cancer incidence. Here, we show that metformin forms stable complexes with copper (II) ions. Both copper(I)/metformin and copper(II)/metformin complexes form adducts with glutathione, the main intracellular antioxidative peptide, found at high levels in cancer cells. Metformin reduces cell number and viability in SW1222 and K562 cells, as well as in K562-200 multidrug-resistant cells. Notably, the antiproliferative effect of metformin is enhanced in the presence of copper ions.

Characterization of antioxidative peptide purified from black eelpout (Lycodes diapterus) hydrolysate

The functional peptides from protein hydrolysates of various fishery sources have been identified such as antioxidant activity. The main intention of this study was purification and characterization of antioxidative peptide from black eelpout muscle. The antioxidative peptides were purified from black eelpout (Lycodes diapterus) muscle using different proteases. Antioxidant activity of black eelpout hydrolysates was evaluated using DPPH radical scavenging activity. Among six hydrolysates, the pepsin hydrolysate had the highest antioxidant activity compared to the other hydrolysates. Therefore, it was further purified and a peptide with seven amino acid residues of DLVKVEA (784 Da) was identified by amino acid sequence analysis. The EC50 value for scavenging DPPH radicals by purified peptide was 688.77 μM. Additionally, the purified peptide exhibited protective effect against DNA damage induces by oxidation in mouse macrophages (RAW 264.7 cells). The results of this study suggest that black eelpout muscle protein hydrolysate could potentially contribute to development of bioactive peptides in basic research.

Antioxidative Peptides from Proteolytic Hydrolysates of False Abalone (Volutharpa ampullacea perryi): Characterization, Identification, and Molecular Docking

Antioxidative peptides were produced from false abalone (Volutharpa ampullacea perryi) using enzymatic hydrolysis. Trypsin produced the most bioactive hydrolysates with the highest scavenging ABTS+• free radicals compared to pepsin, alcalase, neutrase, and flavourzyme. The response surface methodology studies on trypsin hydrolysis indicated that the hydrolysis temperature, time, and pH were interacted with each other (p < 0.05), and the optimal conditions were hydrolysis at 51.8 °C for 4.1 h, pH 7.7 and the maximum predicted hydrolysis degree was 13.18% and ABTS+• scavenging activity of 79.42%. The optimized hydrolysate was subjected to ultrafiltration fractionation, and the fraction with MW < 3 kDa showed the highest ABTS+• scavenging activity. There were 193 peptide sequences identified from this peptide fraction and 133 of them were successfully docked onto human myeloperoxidase (MPO), an enzyme involved in forming reactive oxidants in vivo. The highest scored peptide, no. 39, consists of DTETGVPT. Its structure and molecular interactions with MPO active site were compared with previously characterized peptide hLF1-11. The interactions between peptide no. 39 and MPO include electrostatic charge, hydrogen bonds, and covalent bonds. The antioxidative peptide produced in this research may exert antioxidant activity in vivo due to its potential inhibition effect on MPO.