A narrative review of mechanisms of ferroptosis in cancer: new challenges and opportunities

Jiang, Mingyan; Hu, Ruofei; Yu, Ruixin; Tang, Yiwei; Li, Jinrong

doi:10.21037/atm-21-4863

Cited by 14 publications

(11 citation statements)

References 74 publications

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“…SLC7A11 or Xct is a key component of the cystine/glutamate antiporter system that plays a crucial role in cellular antioxidant defenses and leads to ferroptosis in cancer cells . The primary function of the Xc-transporter is to import cystine, by providing cystine, which plays a crucial role in maintaining cellular redox balance and protecting cells from oxidative stress.…”

Section: Resultsmentioning

confidence: 99%

Immunotherapy Study on Non-small-Cell Lung Cancer (NSCLC) Combined with Cytotoxic T Cells and miRNA34a

Pandey,

Chiu,

Wang

2024

Mol. Pharmaceutics

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Immunotherapy has emerged as a promising approach for cancer treatment, and the use of microRNAs (miRNAs) as therapeutic agents has gained significant attention. In this study, we investigated the effectiveness of immunotherapy utilizing miRNA34a and Jurkat T cells in inducing cell death in non-small-cell lung cancer cells, specifically A549 cells. Moreover, we explored the impact of Jurkat T cell activation and miRNA34a delivery using iron oxide nanorods (IONRs) on the killing of cancer cells. A549 cells were cocultured with both activated and inactivated Jurkat T cells, both before and after the delivery of miRNA34a. Surprisingly, our results revealed that even inactive Jurkat T cells were capable of inducing cell death in cancer cells. This unexpected observation suggested the presence of alternative mechanisms by which Jurkat T cells can exert cytotoxic effects on cancer cells. We stimulated Jurkat T cells using anti-CD3/CD28 and analyzed their efficacy in killing A549 compared to that of the inactive Jurkat T cells in conjunction with miRNA34a. Our findings indicated that the activation of Jurkat T cells significantly enhanced their cytotoxic potential against cancer cells compared to their inactive counterparts. The combined treatment of A549 cells with activated Jurkat T cells and miRNA34a demonstrated the highest level of cancer cell death, suggesting a synergistic effect between Jurkat T cell activation and miRNA therapy. Besides the apoptosis mechanism for the Jurkat T cells' cytotoxic effects on A549 cells, we furthermore investigated the ferroptosis pathway, which was found to have an impact on the cancer cell killing due to the presence of miRNA34a and IONRs as the delivery agent inside the cancer cells.

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Section: Resultsmentioning

confidence: 99%

Immunotherapy Study on Non-small-Cell Lung Cancer (NSCLC) Combined with Cytotoxic T Cells and miRNA34a

Pandey,

Chiu,

Wang

2024

Mol. Pharmaceutics

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“…Ferroptosis shows unique morphological characteristics, such as mitochondrial atrophy and increased mitochondrial membrane density. The physiological function of ferroptosis is lacking and remains to be discovered, and in recent years, much effort has focused on investigating the potential mechanism of ferroptosis (12)(13)(14). The influencing factors of ferroptosis include iron, lipid reactive oxygen species, and glutathione peroxidase 4 (GPX4).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of the relationship between the ferroptosis and tumor-infiltrating immune cells, mutation, and immunotherapy in breast cancer

He¹,

Zhou²,

Wang³

et al. 2022

Ann Transl Med

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Background Ferroptosis is a kind of programmed cell death that is characterized by iron dependence. It differs from apoptosis, necrosis, autophagy, pyroptosis, and other types of cell death. Some studies have found that most of the genes involved in the regulation of ferroptosis or act as markers of ferroptosis are related to the poor prognosis of cancer patients. Methods This study evaluated the expression, mutation, and copy number variation (CNV) of 60 previously reported ferroptosis genes in breast cancer samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Unsupervised clustering of breast cancer samples with ferroptosis genes was performed, followed by enrichment analysis with Gene Set Variation Analysis (GSVA), mutation display, and correlation analysis of clinical characteristics. Based on the analysis of differences among groups, the ferroptosis-related genes were identified, and the consistent clustering of breast cancer samples was performed. The characteristic genes were screened by stochastic forest algorithm and COX analysis, and a ferroptosis score (ferr.score) model was constructed to evaluate the prognosis of breast cancer patients. Results Copy number amplification and deletion of ferroptosis genes are common in breast cancer. Breast cancer patients grouped by ferroptosis gene clusters showed significant differences in survival, immune cell infiltration, and enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways. The ferroptosis-related differential genes were identified by comparison among clustering groups of ferroptosis gene. Characteristic genes were screened from these ferroptosis-related differential genes to construct the ferr.score model. The scoring model could accurately distinguish and predict the survival prognosis and immunotherapy efficacy in breast cancer patients. Conclusions Ferroptosis plays an important role in the occurrence and development of tumors. According to the ferr.score model, the breast cancer samples can be divided into two groups with significantly different prognoses. These results provide novel insights and ideas for immunotherapy in breast cancer patients.

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“…General characteristics of ferroptosis include moderate condensation of chromatin, ruptured mitochondrial outer membrane, mitochondrial atrophy, cytoplasmic swelling, and loss of plasma membrane integrity [ 94 ]. On the other hand, typical biochemical characteristics of ferroptosis include GPX4 inactivation, GSH depletion, and cystine deficiency [ 95 ]. It has been demonstrated that ferroptosis plays a role in neurodegeneration [ 96 , 97 , 98 ].…”

Section: Mechanisms Of Apoptosismentioning

confidence: 99%

Potential of Therapeutic Small Molecules in Apoptosis Regulation in the Treatment of Neurodegenerative Diseases: An Updated Review

Dailah

2022

Molecules

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Neurodegenerative disorders (NDs) include Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS) and the common feature of NDs is the progressive death of specific neurons in the brain. Apoptosis is very important in developing the nervous system, nonetheless an elevated level of cell death has been observed in the case of NDs. NDs are different in terms of their neuronal vulnerability and clinical manifestations, however they have some overlapping neurodegenerative pathways. It has been demonstrated by several studies with cell lines and animal models that apoptosis has a significant contribution to make in advancing AD, ALS, HD, and PD. Numerous dying neurons were also identified in the brains of individuals with NDs and these conditions were found to be linked with substantial cell loss along with common characteristics of apoptosis including activation of caspases and cysteine-proteases, DNA fragmentation, and chromatin condensation. It has been demonstrated that several therapeutic agents including antioxidants, minocycline, GAPDH ligands, p53 inhibitors, JNK (c-Jun N-Terminal Kinase) inhibitors, glycogen synthase kinase-3 inhibitor, non-steroidal anti-inflammatory drugs, D2 dopamine receptor agonists, FK506, cell cycle inhibitors, statins, drugs targeting peroxisome proliferator-activated receptors, and gene therapy have the potential to provide protection to neurons against apoptosis. Therefore, the use of these potential therapeutic agents might be beneficial in the treatment of NDs. In this review, we have summarized the pathways that are linked with apoptotic neuronal death in the case of various NDs. We have particularly focused on the therapeutic agents that have neuroprotective properties and the potential to regulate apoptosis in NDs.

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A narrative review of mechanisms of ferroptosis in cancer: new challenges and opportunities

Cited by 14 publications

References 74 publications

Immunotherapy Study on Non-small-Cell Lung Cancer (NSCLC) Combined with Cytotoxic T Cells and miRNA34a

Immunotherapy Study on Non-small-Cell Lung Cancer (NSCLC) Combined with Cytotoxic T Cells and miRNA34a

Comprehensive analysis of the relationship between the ferroptosis and tumor-infiltrating immune cells, mutation, and immunotherapy in breast cancer

Potential of Therapeutic Small Molecules in Apoptosis Regulation in the Treatment of Neurodegenerative Diseases: An Updated Review

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