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Article

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

by
Sherin Abdelrahman
1,
Mawadda Alghrably
2,
Marcello Campagna
3,
Charlotte Armgard Emma Hauser
1,*,
Mariusz Jaremko
1,* and
Joanna Izabela Lachowicz
3,*
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
*
Authors to whom correspondence should be addressed.
Molecules 2021, 26(16), 4730; https://doi.org/10.3390/molecules26164730
Submission received: 9 July 2021 / Revised: 27 July 2021 / Accepted: 29 July 2021 / Published: 5 August 2021
(This article belongs to the Special Issue Old Drugs for New Metal-Related Diseases)
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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.
Keywords: metformin; copper complexes; diabetes; cancer; proliferation; protonation constants; stability constants; glutathione; NMR metformin; copper complexes; diabetes; cancer; proliferation; protonation constants; stability constants; glutathione; NMR

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MDPI and ACS Style

Abdelrahman, S.; Alghrably, M.; Campagna, M.; Hauser, C.A.E.; Jaremko, M.; Lachowicz, J.I. Metal Complex Formation and Anticancer Activity of Cu(I) and Cu(II) Complexes with Metformin. Molecules 2021, 26, 4730. https://doi.org/10.3390/molecules26164730

AMA Style

Abdelrahman S, Alghrably M, Campagna M, Hauser CAE, Jaremko M, Lachowicz JI. Metal Complex Formation and Anticancer Activity of Cu(I) and Cu(II) Complexes with Metformin. Molecules. 2021; 26(16):4730. https://doi.org/10.3390/molecules26164730

Chicago/Turabian Style

Abdelrahman, Sherin, Mawadda Alghrably, Marcello Campagna, Charlotte Armgard Emma Hauser, Mariusz Jaremko, and Joanna Izabela Lachowicz. 2021. "Metal Complex Formation and Anticancer Activity of Cu(I) and Cu(II) Complexes with Metformin" Molecules 26, no. 16: 4730. https://doi.org/10.3390/molecules26164730

APA Style

Abdelrahman, S., Alghrably, M., Campagna, M., Hauser, C. A. E., Jaremko, M., & Lachowicz, J. I. (2021). Metal Complex Formation and Anticancer Activity of Cu(I) and Cu(II) Complexes with Metformin. Molecules, 26(16), 4730. https://doi.org/10.3390/molecules26164730

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