Work

Mitochondria-Targeted Titanium Complex Exerts Potent Anticancer Activity by Disturbing Iron Homeostasis

Year: 2025

Type: article

Abstract: Triple-negative breast cancer (TNBC) is an aggressive malignancy, with limited targeted treatment options. In this study, we developed a novel triphenylphosphine (TPP)-modified deferasirox (DFX) titanium complex ( Ti-DFX-TPP ) to disrupt iron homeostasis in TNBC cells through transmetalation. Ti-DFX-TPP depletes the labile iron pool, triggering a compensatory upregulation of transferrin receptor 1 (TfR1) in response to an intracellular iron deficiency. The disruption of iron metabolism by Ti-DFX-TPP increases reactive oxygen species (ROS) levels, which in turn lead to mitochondrial dysfunction and DNA damage, ultimately inhibiting cancer cell growth. In vivo studies further demonstrated that Ti-DFX-TPP inhibits tumor growth without significant toxicity to major organs. These findings suggest that Ti-DFX-TPP is a promising therapeutic candidate for TNBC, as it exploits the disruption of iron metabolism and ROS pathways to enhance its anticancer efficacy.

Source: ACS Pharmacology & Translational Science

DOI: 10.1021/acsptsci.5c00219

Authors: Qi-Xin Guan, Long-Bo Yu, Peng Wang, Qing-yuan Hu, Cai-Ping Tan

Institution: Sun Yat-sen University

Language: English

Topic: Metal complexes synthesis and properties

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Natural Science Foundation of China, Fundamental Research Funds for the Central Universities, Basic and Applied Basic Research Foundation of Guangdong Province