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Review
. 2022 Aug 11:10:967337.
doi: 10.3389/fchem.2022.967337. eCollection 2022.

Targeting of the intracellular redox balance by metal complexes towards anticancer therapy

María Isabel Murillo  1 , Christian Gaiddon  2 , Ronan Le Lagadec  1
Affiliations
Review

Targeting of the intracellular redox balance by metal complexes towards anticancer therapy

María Isabel Murillo et al. Front Chem. .

Abstract

The development of cancers is often linked to the alteration of essential redox processes, and therefore, oxidoreductases involved in such mechanisms can be considered as attractive molecular targets for the development of new therapeutic strategies. On the other hand, for more than two decades, transition metals derivatives have been leading the research on drugs as alternatives to platinum-based treatments. The success of such compounds is particularly due to their attractive redox kinetics properties, favorable oxidation states, as well as routes of action different to interactions with DNA, in which redox interactions are crucial. For instance, the activity of oxidoreductases such as PHD2 (prolyl hydroxylase domain-containing protein) which can regulate angiogenesis in tumors, LDH (lactate dehydrogenase) related to glycolysis, and enzymes, such as catalases, SOD (superoxide dismutase), TRX (thioredoxin) or GSH (glutathione) involved in controlling oxidative stress, can be altered by metal effectors. In this review, we wish to discuss recent results on how transition metal complexes have been rationally designed to impact on redox processes, in search for effective and more specific cancer treatments.

Keywords: anticancer therapy; oxidoreductases; redox balance; transition metals; tumor metabolism.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Metabolic pathways involved in tumor adaptation to its stressful environment (Gaiddon et al., 2021).
FIGURE 2
FIGURE 2
Platinum complexes used as anticancer drugs.
FIGURE 3
FIGURE 3
Ruthenium complexes studied in clinical trials as candidates for anticancer treatments and palladium compound approved for clinical use.
FIGURE 4
FIGURE 4
Relationship between metabolism and redox signaling in cancer cells (Wang et al., 2019).
FIGURE 5
FIGURE 5
Relationship between redox state of glutathione and regulation of cell function and cell detoxification (Montero and Jassem, 2011).
FIGURE 6
FIGURE 6
Iron complexes able to alter redox enzymatic activity.
FIGURE 7
FIGURE 7
Ruthenium compounds capable to interact with redox enzymes.
FIGURE 8
FIGURE 8
Osmium, rhodium and copper complexes studied as anticancer agents.
FIGURE 9
FIGURE 9
Pt(IV) anticancer drugs that have entered clinical trials (A) and redox interaction of Pt(IV) complexes and glutathione (B).
FIGURE 10
FIGURE 10
Platinum, iridium, silver and gold compounds studied as potential enzymes inhibitors.
See this image and copyright information in PMC

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