Metal Complexes or Chelators with ROS Regulation Capacity: Promising Candidates for Cancer Treatment

Abstract

Reactive oxygen species (ROS) are rapidly eliminated and reproduced in organisms, and they always play important roles in various biological functions and abnormal pathological processes. Evaluated ROS have frequently been observed in various cancers to activate multiple pro-tumorigenic signaling pathways and induce the survival and proliferation of cancer cells. Hydrogen peroxide (H2O2) and superoxide anion (O2•−) are the most important redox signaling agents in cancer cells, the homeostasis of which is maintained by dozens of growth factors, cytokines, and antioxidant enzymes. Therefore, antioxidant enzymes tend to have higher activity levels to maintain the homeostasis of ROS in cancer cells. Effective intervention in the ROS homeostasis of cancer cells by chelating agents or metal complexes has already developed into an important anti-cancer strategy. We can inhibit the activity of antioxidant enzymes using chelators or metal complexes; on the other hand, we can also use metal complexes to directly regulate the level of ROS in cancer cells via mitochondria. In this review, metal complexes or chelators with ROS regulation capacity and with anti-cancer applications are collectively and comprehensively analyzed, which is beneficial for the development of the next generation of inorganic anti-cancer drugs based on ROS regulation. We expect that this review will provide a new perspective to develop novel inorganic reagents for killing cancer cells and, further, as candidates or clinical drugs.

New insights on the application of half‐sandwich complexes with metal–iodide bonds for agricultural fungicides

“…Furthermore, it is conceivable that the observed antifungal activity of this class of complexes originates from the easy removal of iodide ions and the consequent formation of new organometallic compounds that may be the units possessing the observed antifungal property. Indeed, as confirmed by multiple studies, [20][21][22] organometallic complexes could be involved in redox reactions with the generation of reactive free radicals (i.e., reactive oxygen species or reactive nitrogen species) that lead biological systems to oxidative stress. Furthermore, other organometallic complexes, with different metal-halide bonds (different from iodide), lack any antifungal effect.…”

Silver(I) 1,10-Phenanthroline Complexes Are Active against Fonsecaea pedrosoi Viability and Negatively Modulate Its Potential Virulence Attributes

“…As a consequence, they can cause cell death by binding and oxidizing essential molecules, such as proteins, lipids and DNA [ 5 , 87 ]. Thus, the maintenance of intracellular ROS balance is crucial for cellular growth and survival [ 88 , 89 ]. Bearing this in mind, the production of ROS after treatment with the silver(I)-phen complexes was evaluated in order to elucidate the possible mechanisms involved with anti- F. pedrosoi activity.…”

Alteration of the HIF-1α/VEGF Signaling Pathway and Disruption of the Cell Cycle by Second Generation Carbosilan Dendrimers

“…As oxidant, they increase the level of ROS by targeting antioxidant enzyme systems or at the mitochondrial level. 32 Regarding antioxidant properties, as a way to retard oxidative damage, the control of the redox potential of the metal center seems to be crucial. 33 , 34 We show here that both the second-generation carbosilane metallodendrimer G 2 R and its corresponding precursor G 2 P exerted an antioxidant effect on androgen-sensitive as well as on androgen-resistant prostate cancer cells.…”