Can bacteria F. nucleatum be actively involved in colon cancer progression via a radical mediated mechanism?

Outer membrane proteins of Fusobacterium nucleatum, a cancer­leading bacteria, are considered as the factors responsible for its pathogenicity. Among them, homotrimeric autotransporter protein YadA (Yersinia adhesin A) is an important virulence factor also found in the outer membrane of pathogenic Yersinia species. In this paper, the structure and stability of certain Cu(II) complexes with YadA fragments were investigated using both, experimental and theoretical methods. Potentiometry, UV-Vis, CD, EPR, and calculations at the density functional theory (DFT) level were applied to determine the metal ion coordination sphere. Moreover, the complexes ability to DNA cleavage and reactive oxygen species (ROS) production was studied. We have shown that copper(II) complexes can cleave DNA by 1O2, O2•- and •OH, which are formed in the studied systems. However, the results of electrophoretic experiments revealed that complexes cleave DNA less effectively than free copper(II) ions. Therefore, the presence of studied peptides may prevent DNA from a Cu(II)-induced damage to some extent.

What Is the Correlation between Preeclampsia and Cancer? The Important Role of Tachykinins and Transition Metal Ions.

Metal ions are irreplaceable in many biological processes. They are components of numerous metalloproteins and serve as cofactors or structural elements for enzymes. Interestingly, iron, copper and zinc play important roles in accelerating or preventing neoplastic cell transformation. Noteworthily, a lot of proliferative and invasive mechanisms are exploited by both malignant tumors and pregnancy. Cancer cells, as well as developing placenta cells, create a microenvironment supportive of immunologic privilege and angiogenesis. Therefore, pregnancy and cancer progression share many similarities. Moreover, during preeclampsia and cancer, significant changes in relevant trace element concentrations, tachykinin levels, expressions of neurokinin receptors, oxidative stress and angiogenic imbalance are observed. This sheds a new light on the role of metal ions and tachykinins in cancer progression and pregnancy, especially in preeclamptic women.

Interactions of neurokinin B with copper(II) ions and their potential biological consequences.

Preeclampsia is a blood pressure disorder associated with significant proteinuria. Hypertensive women have increased levels of neurokinin B (NKB) and Cu(II) ions in blood plasma during pregnancy. NKB bears the ATCUN/NTS N-terminal motif empowering strong Cu(II) binding in a characteristic four-nitrogen (4N) square-planar motif, but an alternative Cu(II)NKB2 geometry was proposed earlier. We studied the coordination of DMHD-NH2, representing the NKB ATCUN/NTS motif, to Cu(II) by potentiometry, electronic absorption and circular dichroism spectroscopy in water and SDS micellar solutions. NKB was studied in SDS micelles. The experiments were aided by density functional theory (DFT) calculations. We found that under all investigated conditions NKB formed solely 1 : 1 complexes. In the absence of SDS, the 4N complex at physiological pH 7.4 has a very low dissociation constant of 3.5 fM, but the interaction with SDS weakened the binding nearly thousand-fold. This interaction may serve as a molecular switch for specific Cu(II) delivery to membrane receptors by NKB. Furthermore, the calculations based on clinical data indicate a potential toxic role of Cu(II)NKB in preeclampsia.