Work

Ascorbate: a forgotten component in the cytotoxicity of Cu(II) ATCUN peptide complexes

Year: 2024

Type: article

Abstract: -Gly-Gly-His-COOH, GGH) in the presence of ascorbate as an additive. In the following 4 decades, structural modifications of this complex were implemented, however, anticancer activity could not be significantly increased. This has led to neglecting the ATCUN motif and its Cu(II) complexes as potential chemotherapeutic agents. Furthermore, the addition of ascorbate with its positive effect on the anticancer activity has fallen into oblivion. In this work, we compared Cu(II) GGH with Cu(II) ATCUN peptides bearing β-Ala instead of Gly at the 2nd position of the peptide sequence regarding their in vitro complex stability and cytotoxicity (MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and annexin V-FITC (fluorescein isothiocyanate) apoptosis assay) towards three cancer cell lines (AGS, HeLa and NCI-N87). Such an exchange of amino acids led to an up to three-fold higher cytotoxic effect in the presence of ascorbate. We thus achieved a significant increase in the otherwise moderate cytotoxicity of Cu(II) ATCUN-like complexes. Lipophilicity assays (n-octanol/water coefficient, log P values) of the studied complexes were used to evaluate differences in the antiproliferative activity.

Source: JBIC Journal of Biological Inorganic Chemistry

DOI: 10.1007/s00775-024-02083-9

Authors: Julian Heinrich, Elisa Siddiqui, Henrike Eckstein, Michael Naumann, Nora Kulak

Institutions: University of Potsdam, Otto-von-Guericke-Universität Magdeburg

Language: English

Topic: Metal complexes synthesis and properties

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,790