ORCID

Abstract

Cu(II), Mn(II) and Ag(I) complexes incorporating bridging dicarboxylate and 1,10-phenanthroline ligands have exhibited anti-cancer potential with significant in vitro and in vivo cytotoxic efficacies. Our study focuses on regulated cell death process of apoptosis as a mode of action of the anti-cancer activity by the complexes. Cytotoxicity screening of the complexes demonstrated all the metal-dicarboxylate-phenanthroline complexes exhibit superior activity compared to their non-phenanthroline containing precursors, in addition to cisplatin. The Cu(II) and Mn(II) complexes were shown to induce reactive oxygen species (ROS) but this was not observed for the Ag(I) analogues. Furthermore, apoptosis was found to be induced by all the metal-phenanthroline complexes to varying degrees contingent on the type of metal centre in the complex. Apoptotic gene expression analysis established the predominant activation of the intrinsic apoptotic pathway, with co-stimulation of the extrinsic pathway observed in some cases. The mechanistic data provided within this study highlights the multi-modal activity of the metal-phenanthroline complexes contingent on the type of metal present, warranting continued investigation of their biological modes of action beyond apoptosis induction.

Keywords

1, 10-Phenanthroline, Anti-cancer, Apoptosis, Metal complexes, ROS production

Publication Date

2025-01-01

Publication Title

BioMetals

Volume

38

Issue

3

ISSN

0966-0844

First Page

785

Last Page

805

Deposit Date

2026-07-24

Funding

Open Access funding provided by the IReL Consortium. The authors acknowledge financial support received from the Irish Research Council (GOIPG/2021/958).

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.


Share

COinS