4.7 Article

Might Cu(ii) binding, DNA cleavage and radical production by YadA fragments be involved in the promotion of F. nucleatum related cancers?

Journal

DALTON TRANSACTIONS
Volume 51, Issue 18, Pages 7040-7052

Publisher

ROYAL SOC CHEMISTRY
DOI: 10.1039/d2dt00328g

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Funding

  1. Polish National Science Centre [NCN 2014/13/B/ST5/04359]

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In many cases, human microbiota are associated with cancer progression. It was concluded that the bacterium Fusobacterium nucleatum increases neoplastic changes. Recent studies show that metal complexes with outer membrane protein fragments can promote the formation of reactive oxygen species (ROS), leading to oxidative stress and cell damage. This paper characterizes the formation of copper(ii) complexes with fragments of adhesin YadA from F. nucelatum and demonstrates their ability to produce ROS. Importantly, the free ligands are efficient DNA-cleaving agents.
In many cases, human microbiota are associated with cancer progression. It was concluded that Fusobacterium nucleatum increases neoplastic changes. This bacterium is naturally present in human dental plaque. However, if it is present in the colon, it becomes a precursor of cancer. Antibiotic treatment of mice infected with F. nucleatum slowed tumor growth, which agrees with the fundamental role of bacteria in tumorigenesis. Remarkably, recent studies indicate that transition metal complexes with fragments of outer membrane proteins are able to promote reactive oxygen species (ROS) formation and are responsible for oxidative stress, which consequently leads to cell damage. Therefore, in this paper, the formation of copper(ii) complexes with fragments of adhesin YadA from F. nucleatum is characterized. Moreover, the ability of the complexes to produce ROS has been shown. Importantly, free ligands are efficient DNA-cleaving agents.

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