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

• Published in: Molecules (Basel, Switzerland) Vol. 26; no. 16; p. 4730
• Main Authors: Abdelrahman, Sherin, Alghrably, Mawadda, Campagna, Marcello, Hauser, Charlotte Armgard Emma, Jaremko, Mariusz, Lachowicz, Joanna Izabela
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 05.08.2021; MDPI
• Subjects: Adducts; Antidiabetics; Antitumor activity; Cancer; Cancer therapies; Cell cycle; Cell number; Complex formation; Copper; copper complexes; Copper compounds; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Experiments; Health risks; Ions; Kinases; Leukemia; Ligands; Metformin; Multidrug resistance; NMR; Nuclear magnetic resonance; Penicillin; proliferation; protonation constants; Risk analysis; Risk factors; Software; Spectrum analysis; Tumors; New York; United States > US; Germany; NMR; copper complexes; proliferation; protonation constants; glutathione; stability constants; metformin; cancer; diabetes
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules26164730

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.