Abstract
Background: Recently, novel gold(III)-dithiocarbamato peptidomimetics, designed to target peptide transporters upregulated in several tumor cells have shown promise as anticancer agents. Results: The biological behavior of the most promising derivatives AuD8 and AuD9 was studied in PC3 and DU145 prostate cancer cells. They exert higher cytotoxicity in vitro than the reference drug cisplatin and induce apoptosis, promoting mitochondrial membrane permeabilization and stimulating reactive oxygen species generation. Moreover, they inhibit both selenoenzyme thioredoxin reductase and proteasome activity. Additionally, AuD8 effectively reduces tumor growth in prostate tumor-bearing nude mice with minimal systemic toxicity. Conclusion: Altogether, our results provide insights into the anticancer activity of these gold(III)-dithiocarbamato peptidomimetics and support their potential as new agents for prostate cancer treatment.
Financial & competing interests disclosure
The EU (Marie Curie European Re-Integration Grant 204828-PEPMIDAS), Ministero della Salute (Ricerca Finalizzata FSN, I.R.C.C.S., Italy), MIUR (PRIN-2009) and A.R.TE.M.O. Association are acknowledged for their financial support. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Ethical conduct of research
The authors state that all studies involving animal testing were carried out in accordance with the ethical guidelines for animal research acknowledging the Italian Regulation and the European Directive 86/609/EEC as to the animal welfare and protection, and the related codes of practice.