The crosstalk effect between ferrous and other ions metabolism in ferroptosis for therapy of cancer

Ke, Kun; Li, Li; Lü, Chao; Zhu, Qing; Mou, Yiping; Wang, Hui-Ju; Jin, Weiwei

doi:10.3389/fonc.2022.916082

Cited by 17 publications

(11 citation statements)

References 153 publications

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“…Additionally, mutations in FSP1 can impact its resistance to ferroptosis, highlighting the potential therapeutic relevance of targeting this pathway for diseases associated with ferroptosis, including cancers (Hadian, 2020;Ke et al, 2022).…”

Section: Fsp1-nad(p)h-coq10 Pathwaymentioning

confidence: 99%

“…This pathway operates independently of the traditional ferroptosis regulator, GPX4, challenging the previous understanding of ferroptosis mechanisms. Additionally, mutations in FSP1 can impact its resistance to ferroptosis, highlighting the potential therapeutic relevance of targeting this pathway for diseases associated with ferroptosis, including cancers (Hadian, 2020; Ke et al, 2022).…”

Section: Overview Of Ferroptosis In Cancermentioning

confidence: 99%

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Induction of ferroptosis by natural phenols: A promising strategy for cancer therapy

Zhang,

Xie

2024

Phytotherapy Research

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In recent years, heightened interest surrounds the exploration of natural phenols as potential agents for cancer therapy, specifically by inducing ferroptosis, a unique form of regulated cell death characterized by iron‐dependent lipid peroxidation. This review delves into the roles of key natural phenols, flavonoids, phenolic acids, curcumin, and stilbenes, in modulating ferroptosis and their underlying mechanisms. Emphasizing the significance of amino acid, lipid, and iron metabolism, the study elucidates the diverse pathways through which these phenols regulate ferroptosis. Notably, curcumin, a well‐known polyphenol, exhibits multifaceted interactions with cellular components involved in ferroptosis regulation, providing a distinctive therapeutic avenue. Stilbenes, another phenolic class, demonstrate promising potential in influencing lipid metabolism and iron‐dependent processes, contributing to ferroptotic cell death. Understanding the intricate interplay between these natural phenols and ferroptosis not only illuminates complex cellular regulatory networks but also unveils potential avenues for novel cancer therapies. Exploring these compounds as inducers of ferroptosis presents a promising strategy for targeted cancer treatment, capitalizing on the delicate balance between cellular metabolism and regulated cell death mechanisms. This article synthesizes current knowledge, aiming to stimulate further research into the therapeutic potential of natural phenols in the context of ferroptosis‐mediated cancer therapy.

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Section: Fsp1-nad(p)h-coq10 Pathwaymentioning

confidence: 99%

Section: Overview Of Ferroptosis In Cancermentioning

confidence: 99%

Induction of ferroptosis by natural phenols: A promising strategy for cancer therapy

Zhang,

Xie

2024

Phytotherapy Research

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“…The interaction between iron and other mineral ions, including calcium, is known to be linked to the production of reactive oxygen species (ROS) and the process of ferroptosis, which is attributed to the Fenton reaction [142,161]. Calcium, in particular, has been found to exacerbate iron-mediated ROS generation, especially in the context of neurodegenerative diseases [162][163][164][165].…”

Section: Iron and Calcium Ros Generation And Ferroptosismentioning

confidence: 99%

Calcium’s Role and Signaling in Aging Muscle, Cellular Senescence, and Mineral Interactions

Terrell,

Choi,

Choi

2023

IJMS

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Calcium research, since its pivotal discovery in the early 1800s through the heating of limestone, has led to the identification of its multi-functional roles. These include its functions as a reducing agent in chemical processes, structural properties in shells and bones, and significant role in cells relating to this review: cellular signaling. Calcium signaling involves the movement of calcium ions within or between cells, which can affect the electrochemical gradients between intra- and extracellular membranes, ligand binding, enzyme activity, and other mechanisms that determine cell fate. Calcium signaling in muscle, as elucidated by the sliding filament model, plays a significant role in muscle contraction. However, as organisms age, alterations occur within muscle tissue. These changes include sarcopenia, loss of neuromuscular junctions, and changes in mineral concentration, all of which have implications for calcium’s role. Additionally, a field of study that has gained recent attention, cellular senescence, is associated with aging and disturbed calcium homeostasis, and is thought to affect sarcopenia progression. Changes seen in calcium upon aging may also be influenced by its crosstalk with other minerals such as iron and zinc. This review investigates the role of calcium signaling in aging muscle and cellular senescence. We also aim to elucidate the interactions among calcium, iron, and zinc across various cells and conditions, ultimately deepening our understanding of calcium signaling in muscle aging.

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“…Several major advances have occurred in the last few years in relation to iron metabolism and the identification of a number of new anticancer drug targets, which, in addition to the inhibition of DNA synthesis and of free radical toxicity, involve various new carcinogenic molecules, as well as different biomolecules and metabolic pathways [24][25][26][27][28]. These include, for example, ferroptosis, macrophage anticancer activity effects, hyperferritinemia, hypoxia-inducible factor (HIF), iron-related carcinogenic molecules, toxins found in food, etc.…”

Section: Introductionmentioning

confidence: 99%

“…These include, for example, ferroptosis, macrophage anticancer activity effects, hyperferritinemia, hypoxia-inducible factor (HIF), iron-related carcinogenic molecules, toxins found in food, etc. Selective modulation for achieving anticancer effects could be accomplished in most of these cases by adopting new drug-targeting strategies, including chelating drugs with specific properties and physicochemical characteristics [8,22,[24][25][26][27][28].…”

Section: Introductionmentioning

confidence: 99%

New Iron Metabolic Pathways and Chelation Targeting Strategies Affecting the Treatment of All Types and Stages of Cancer

Kontoghiorghes¹

2022

IJMS

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There is new and increasing evidence from in vitro, in vivo and clinical studies implicating the pivotal role of iron and associated metabolic pathways in the initiation, progression and development of cancer and in cancer metastasis. New metabolic and toxicity mechanisms and pathways, as well as genomic, transcription and other factors, have been linked to cancer and many are related to iron. Accordingly, a number of new targets for iron chelators have been identified and characterized in new anticancer strategies, in addition to the classical restriction of/reduction in iron supply, the inhibition of transferrin iron delivery, the inhibition of ribonucleotide reductase in DNA synthesis and high antioxidant potential. The new targets include the removal of excess iron from iron-laden macrophages, which affects anticancer activity; the modulation of ferroptosis; ferritin iron removal and the control of hyperferritinemia; the inhibition of hypoxia related to the role of hypoxia-inducible factor (HIF); modulation of the function of new molecular species such as STEAP4 metalloreductase and the metastasis suppressor N-MYC downstream-regulated gene-1 (NDRG1); modulation of the metabolic pathways of oxidative stress damage affecting mitochondrial function, etc. Many of these new, but also previously known associated iron metabolic pathways appear to affect all stages of cancer, as well as metastasis and drug resistance. Iron-chelating drugs and especially deferiprone (L1), has been shown in many recent studies to fulfill the role of multi-target anticancer drug linked to the above and also other iron targets, and has been proposed for phase II trials in cancer patients. In contrast, lipophilic chelators and their iron complexes are proposed for the induction of ferroptosis in some refractory or recurring tumors in drug resistance and metastasis where effective treatments are absent. There is a need to readdress cancer therapy and include therapeutic strategies targeting multifactorial processes, including the application of multi-targeting drugs involving iron chelators and iron–chelator complexes. New therapeutic protocols including drug combinations with L1 and other chelating drugs could increase anticancer activity, decrease drug resistance and metastasis, improve treatments, reduce toxicity and increase overall survival in cancer patients.

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The crosstalk effect between ferrous and other ions metabolism in ferroptosis for therapy of cancer

Cited by 17 publications

References 153 publications

Induction of ferroptosis by natural phenols: A promising strategy for cancer therapy

Induction of ferroptosis by natural phenols: A promising strategy for cancer therapy

Calcium’s Role and Signaling in Aging Muscle, Cellular Senescence, and Mineral Interactions

New Iron Metabolic Pathways and Chelation Targeting Strategies Affecting the Treatment of All Types and Stages of Cancer

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