Therapeutic potential of the phosphino Cu(I) complex (HydroCuP) in the treatment of solid tumors View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

Valentina Gandin, Cecilia Ceresa, Giovanni Esposito, Stefano Indraccolo, Marina Porchia, Francesco Tisato, Carlo Santini, Maura Pellei, Cristina Marzano

ABSTRACT

[Cu(thp)4][PF6] (HydroCuP) is a phosphino copper(I) complex highly soluble and stable in physiological media that has been developed as a possible viable alternative to platinum-based drugs for anticancer therapy. HydroCuP potently inhibited the growth of human cancer cells derived from solid tumors by inducing endoplasmatic reticulum (ER) stress thus leading to cell death through paraptosis with a preferential efficacy against cancer rather than non-cancer cells. Aim of the present study was to assess the therapeutic potential of HydroCuP in vivo, in syngenic and xenograft murine models of solid tumors by triggering the Unfolded Protein Response (UPR) pathway. With respect to platinum drugs, HydroCuP induced a markedly higher reduction of tumor growth associated with minimal animal toxicity. In human colorectal cancer xenografts, chemotherapy with HydroCuP was extremely effective in both oxaliplatin-sensitive and resistant models. The favorable in vivo tolerability of HydroCuP was also correlated to an encouraging biodistribution profile. Additionally, no signs of drug-related neurotoxicity and nephrotoxicity were observed. Altogether, these results demonstrate that HydroCuP appears worth of further investigation to evaluate its therapeutic activity towards a broad spectrum of solid malignancies. More... »

PAGES

13936

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-017-13698-1

DOI

http://dx.doi.org/10.1038/s41598-017-13698-1

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1092277103

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29066771


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