Unveiling the promising anticancer effect of copper-based compounds: a comprehensive review

Abstract

Copper is a necessary micronutrient for maintaining the well-being of the human body. The biological activity of organic ligands, especially their anticancer activity, is often enhanced when they coordinate with copper(I) and (II) ions. Copper and its compounds are capable of inducing tumor cell death through various mechanisms of action, including activation of apoptosis signaling pathways by reactive oxygen species (ROS), inhibition of angiogenesis, induction of cuproptosis, and paraptosis. Some of the copper complexes are currently being evaluated in clinical trials for their ability to map tumor hypoxia in various cancers, including locally advanced rectal cancer and bulky tumors. Several studies have shown that copper nanoparticles can be used as effective agents in chemodynamic therapy, phototherapy, hyperthermia, and immunotherapy. Despite the promising anticancer activity of copper-based compounds, their use in clinical trials is subject to certain limitations. Elevated copper concentrations may promote tumor growth, angiogenesis, and metastasis by affecting cellular processes.

Experimental and Computational Studies on the Interaction of DNA with Hesperetin Schiff Base CuII Complexes

“…Moreover, the interest in the potential uses of copper in medicine has increased in the last twenty years, and several compounds have been tested, both in vitro and in vivo, as potential anticancer drugs [15][16][17][18][19][20][21]. The observation that tumor growth and metastasis require a higher demand for copper has given an extra boost to the research of Cu-related diagnostics and treatments in the fight against cancer [22][23][24][25]. Today, copper is one of the most widely used metals of the first transition series to develop anticancer drugs due to its redox nature, biocompatible properties, and high effectiveness in inducing cancer cell death [22,26].…”

“…The combination of copper or copper-gluconato with disulfiram (tetraethylthiuram disulfide) was proposed against various tumors and for newly diagnosed glioblastoma multiform (phase 2, identifier NCT03363659) [28,30], metastatic pancreatic cancer (phase 2, NCT03714555), and metastatic breast cancer (phase 2, NCT03323346). The species Cu-ATSM, with ATSM being diacetylbis(4-methyl-3-thiosemicarbazone), is not only under phase 2 of clinical trials for the treatment of rectal cancer (NCT03951337) [25], but has also progressed to phase 2/3 (NCT04082832) for its use against the neurodegenerative disease amyotrophic lateral sclerosis [31]. The complex 64 Cu-DOTA, where DOTA is 2,2 ′ ,2 ′′ ,2 ′′′ -(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetate, reached phase 1 (NCT02708511) for positron emission tomographycomputed tomography use in imaging patients with ovarian and breast cancer [32].…”