Work

Investigation of the Putative Relationship Between Copper Transport and the Anticancer Activity of Cisplatin in Ductal Pancreatic Adenocarcinoma

Year: 2025

Type: article

Abstract: Pancreatic ductal adenocarcinoma (PDAC) is a highly heterogeneous cancer with a severe stromal reaction mediated by pancreatic stellate cells (PSCs), leading to increased resistance to chemotherapy and radiotherapy. Following a repurposing concept, this preclinical study investigates the potential of approved drugs, known to be modulators of cellular copper transport, in combination with cisplatin for therapeutic approaches in PDAC. Two major strategies were pursued: (i) inhibiting copper transporters ATP7A and B with tranilast (TR) and omeprazole (OM) to block the cellular copper and, potentially, also cisplatin efflux, and (ii) using the chelator elesclomol (ES) to elevate intracellular copper and cisplatin levels. Human cell lines PanC-1 (PDAC), HPaSteC (PSC), and their co-culture, as well as the hepatocellular carcinoma cell line HepG2 as a reference model, were used. In addition to an analysis of the expression of copper transport proteins, the dynamics of cellular copper uptake and transport were monitored using a [64Cu]CuCl2 radiotracer approach. In vitro, all drugs enhanced cellular copper uptake and/or reduced copper efflux. Moreover, all drugs contributed to the enhanced cellular anticancer activity of cisplatin, with ES being the most effective compound. The results suggest that the targeted modulation of copper transport mechanisms may offer novel adjuvant approaches for the treatment of PDAC.

Source: Cells

DOI: 10.3390/cells14191489

Authors: Alina Doctor, Jonas Schädlich, Sandra Hauser, Jens Pietzsch

Institutions: Helmholtz-Zentrum Dresden-Rossendorf, Technische Universität Dresden

Language: English

Topic: Trace Elements in Health

Subfield: Nutrition and Dietetics

Field: Nursing

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,258