Ferroptosis at the crossroads of tumor-host interactions, metastasis, and therapy response

Yao, Yinan; Shi, Yuxin; Gao, Zhendong; Sun, Yutong; Yao, Fan; Ma, Li

doi:10.1152/ajpcell.00148.2022

Cited by 12 publications

(6 citation statements)

References 87 publications

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“…All the findings indicated that eriocitrin could give rise to ferroptosis-inducing effects. Alternatively, it strengthens the notion that ferroptosis can be irritated to exert potent antitumor activity [30,31].…”

Section: Discussionsupporting

confidence: 66%

Eriocitrin inhibits epithelial-mesenchymal transformation (EMT) in lung adenocarcinoma cells via triggering ferroptosis

Gao,

Lai,

Deng

et al. 2023

Aging

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Introduction: Lung adenocarcinoma (LUAD) is the most prevalent pathological subtype of non-small cell lung cancer (NSCLC), characterized by a high propensity for relapse and metastasis due to epithelial-mesenchymal transition (EMT) of cancer cells. Ferroptosis, a newly discovered regulated cell death modality, is interconnected with the EMT process in certain cancers. Eriocitrin, a natural flavonoid compound, exerts anti-inflammatory and anticancer effects. Objectives: The aim of this study is to investigate the potential inhibitory effect of eriocitrin on lung adenocarcinoma metastasis and explore whether its underlying mechanism involves ferroptosis induction in cancer cells. Methods: The CCK8 assay and wound healing assay and transwell were conducted to determine the cell viability and migration ability of A549 and H1299 cells, respectively. EMT process was assessed by western blot and RT-PCR to detect protein and mRNA levels of EMT markers. ROS and cell iron were measured to determine ferroptosis level. Results: Eriocitrin treatment significantly inhibited cell viability and migration ability in a concentration-dependent manner. Furthermore, eriocitrin administration for 24 hours resulted in enhanced expression of E-cadherin, while downregulating vimentin, N-cadherin and snail expression, indicating marked repression of the EMT process. Additionally, eriocitrin significantly induced ferroptosis in A549 and H1299 cells, as evidenced by increased ROS levels, downregulation of Nrf-2, SLC7A11 and GPX4 expression, and enhanced cellular iron accumulation. Moreover, pretreatment with the ferroptosis inhibitor ferrostatin-1 effectively abrogated the inhibitory effects of eriocitrin on EMT. Conclusions: Our findings further support the anti-cancer properties of eriocitrin, as evidenced by its ability to inhibit the EMT process in LUAD cells, which is partially mediated through induction of ferroptosis in cancer cells.

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Section: Discussionsupporting

confidence: 66%

Eriocitrin inhibits epithelial-mesenchymal transformation (EMT) in lung adenocarcinoma cells via triggering ferroptosis

Gao,

Lai,

Deng

et al. 2023

Aging

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“…These factors can regulate hypoxia in the tumor microenvironment and promote the generation of ROS, which can play a good therapeutic effect on tumors [13]. Secondly, MW, as an electromagnetic wave from 900 MHz to 2450 MHz, can also be used for tumor ablation therapy in clinical practice [40]. On the one hand, microwave ablation therapy can directly destroy the tumor, on the other hand, it can increase the blood ow to the tumor through heating, and improve the sensitivity of the tumor to PDT, chemotherapy, immunotherapy and radiotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…Previous literature has reported that inhibiting ferroptosis promotes metastasis in breast cancer, clear cell renal cell carcinoma, and melanoma [40]. Therefore, we hypothesized that increased PTK2B expression promoting CRC metastasis may involve ferroptosis inhibition.…”

Section: Ptk2b Is a Key Negative Regulator Of Ferroptosis In Crcmentioning

confidence: 94%

Copper-cysteamine nanoparticle-mediated microwave dynamic therapy promotes colorectal cancer metastasis by inhibiting promoting ferroptosis via downregulating PTK2B

Zhou,

Zhang,

Liu

et al. 2024

Preprint

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Cancer metastasis stands as the primary cause of cancer-related deaths. Recent studies highlight the role of ferroptosis in inhibiting cancer metastasis. In our prior research, we discovered that Cu-Cy-mediated Microwave Dynamic Therapy (MWDT) triggered ferroptosis in colorectal cancer (CRC) cells, leading to reduced cell proliferation. However, the impact of MWDT on tumor metastasis remains unclear, as does the mechanism behind induced iron death. This study aimed to elucidate the effects of MWDT on CRC cell metastasis and uncover the underlying mechanisms. Our findings reveal that MWDT effectively suppresses CRC cell metastasis and significantly decreases PTK2B expression. Functional analyses demonstrate that altering PTK2B expression levels can modulate CRC cell proliferation, migration, and invasion. Further investigations unveil PTK2B's regulation of GPX4 and ACSL4 expression, which in turn influences LPO and MDA levels. Targeted overexpression of PTK2B attenuates MWDT's pro-ferroptosis effect and partially reverses its inhibitory effects on tumor cell metastasis and proliferation. Collectively, these results suggest that MWDT inhibits CRC progression and metastasis through PTK2B-mediated ferroptosis, presenting a novel therapeutic approach for metastatic cancer.

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“…For example, combination therapies of chelators or chelators with other anticancer agents could be used in initiating ferroptosis in relation to drug resistance to established therapies. In these cases, the regulation of ferroptosis appears to offer therapeutic solutions for refractory and recurring tumors in almost all types of cancer, metastasis and drug resistance [143][144][145][146][147][148][149][150][151]. In other cases, such as in therapeutic combination with immunotherapy, ferroptosis can be enhanced and improve the efficacy of immunotherapy [152][153][154].…”

Section: Ferroptosis the New Target In Cancer Therapies And The Role ...mentioning

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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Ferroptosis at the crossroads of tumor-host interactions, metastasis, and therapy response

Cited by 12 publications

References 87 publications

Eriocitrin inhibits epithelial-mesenchymal transformation (EMT) in lung adenocarcinoma cells via triggering ferroptosis

Eriocitrin inhibits epithelial-mesenchymal transformation (EMT) in lung adenocarcinoma cells via triggering ferroptosis

Copper-cysteamine nanoparticle-mediated microwave dynamic therapy promotes colorectal cancer metastasis by inhibiting promoting ferroptosis via downregulating PTK2B

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

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