Metal Complex Formation and Anticancer Activity of Cu(I) and Cu(II) Complexes with Metformin |
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| Authors: | Sherin Abdelrahman Mawadda Alghrably Marcello Campagna Charlotte Armgard Emma Hauser Mariusz Jaremko Joanna Izabela Lachowicz |
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| Affiliation: | 1.Laboratory for Nanomedicine, Division of Biological and Environmental Science and Engineering, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia;2.Division of Biological and Environmental Sciences and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia;3.Department of Medical Sciences and Public Health, University of Cagliari, Policlinico Universitario, 09124 Cagliari, Italy; |
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| Abstract: | 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. |
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| Keywords: | metformin copper complexes diabetes cancer proliferation protonation constants stability constants glutathione NMR |
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