Ferroptosis, a therapeutic target for cardiovascular diseases, neurodegenerative diseases and cancer DOI Creative Commons
Yinghui Li, Cui-Yun Liu, Bo Fang

et al.

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Dec. 22, 2024

The identification of ferroptosis represents a pivotal advancement in the field cell death research, revealing an entirely novel mechanism cellular demise and offering new insights into initiation, progression, therapeutic management various diseases. Ferroptosis is predominantly induced by intracellular iron accumulation, lipid peroxidation, or impairments antioxidant defense system, culminating membrane rupture consequent death. Studies have associated with wide range diseases, enhancing our comprehension its underlying mechanisms, we can formulate innovative strategies, thereby providing renewed hope for patients.

Language: Английский

Ferroptosis in cancer: From molecular mechanisms to therapeutic strategies DOI Creative Commons
Qian Zhou,

Yu Meng,

Daishi Li

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 8, 2024

Ferroptosis is a non-apoptotic form of regulated cell death characterized by the lethal accumulation iron-dependent membrane-localized lipid peroxides. It acts as an innate tumor suppressor mechanism and participates in biological processes tumors. Intriguingly, mesenchymal dedifferentiated cancer cells, which are usually resistant to apoptosis traditional therapies, exquisitely vulnerable ferroptosis, further underscoring its potential treatment approach for cancers, especially refractory cancers. However, impact ferroptosis on extends beyond direct cytotoxic effect cells. induction not only inhibits but also promotes development due negative anticancer immunity. Thus, comprehensive understanding role crucial successful translation therapy from laboratory clinical applications. In this review, we provide overview recent advancements cancer, covering molecular mechanisms, functions, regulatory pathways, interactions with microenvironment. We summarize applications immunotherapy, radiotherapy, systemic therapy, well inhibition various conditions. finally discuss markers, current challenges future directions cancer.

Language: Английский

Citations

153
Ferroptosis: principles and significance in health and disease DOI Creative Commons
Fangquan Chen, Rui Kang, Daolin Tang

et al.

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: June 6, 2024

Abstract Ferroptosis, an iron-dependent form of cell death characterized by uncontrolled lipid peroxidation, is governed molecular networks involving diverse molecules and organelles. Since its recognition as a non-apoptotic pathway in 2012, ferroptosis has emerged crucial mechanism numerous physiological pathological contexts, leading to significant therapeutic advancements across wide range diseases. This review summarizes the fundamental mechanisms regulatory pathways underlying ferroptosis, including both GPX4-dependent -independent antioxidant mechanisms. Additionally, we examine involvement various conditions, cancer, neurodegenerative diseases, sepsis, ischemia–reperfusion injury, autoimmune disorders, metabolic disorders. Specifically, explore role response chemotherapy, radiotherapy, immunotherapy, nanotherapy, targeted therapy. Furthermore, discuss pharmacological strategies for modulating potential biomarkers monitoring this process. Lastly, elucidate interplay between other forms regulated death. Such insights hold promise advancing our understanding context human health disease.

Language: Английский

Citations

51
cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment DOI Creative Commons
Hongying Zhang, Yongliang Liu,

Jieya Liu

et al.

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: Jan. 17, 2024

Cancer is a complex disease resulting from abnormal cell growth that induced by number of genetic and environmental factors. The tumor microenvironment (TME), which involves extracellular matrix, cancer-associated fibroblasts (CAF), tumor-infiltrating immune cells angiogenesis, plays critical role in progression. Cyclic adenosine monophosphate (cAMP) second messenger has pleiotropic effects on the TME. downstream effectors cAMP include cAMP-dependent protein kinase (PKA), exchange activated (EPAC) ion channels. While can activate PKA or EPAC promote cancer growth, it also inhibit proliferation survival context- type-dependent manner. Tumor-associated stromal cells, such as CAF release cytokines factors either stimulate production within Recent studies have shown targeting signaling TME therapeutic benefits cancer. Small-molecule agents adenylate cyclase been to growth. In addition, cAMP-elevating agents, forskolin, not only induce death, but directly some types. this review, we summarize current understanding biology immunology discuss basis for its context-dependent dual oncogenesis. Understanding precise mechanisms interact will be development effective therapies. Future aimed at investigating cAMP-cancer axis regulation may provide new insights into underlying tumorigenesis lead novel strategies.

Language: Английский

Citations

35
Complex roles of autophagy in cancer development, immune evasion, and drug resistance DOI

Xuegang Niu,

Qi Sheng You, Kejun Hou

et al.

Drug Resistance Updates, Journal Year: 2024, Volume and Issue: 78, P. 101170 - 101170

Published: Nov. 15, 2024

Language: Английский

Citations

17
Ferroptosis and pyroptosis are connected through autophagy: a new perspective of overcoming drug resistance DOI Creative Commons
Peng Zhao,

Shuangshuang Yin,

Yuling Qiu

et al.

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 17, 2025

Drug resistance is a common challenge in clinical tumor treatment. A reduction drug sensitivity of cells often accompanied by an increase autophagy levels, leading to autophagy-related resistance. The effectiveness combining chemotherapy drugs with inducers/inhibitors has been widely confirmed, but the mechanisms are still unclear. Ferroptosis and pyroptosis can be affected various types autophagy. Therefore, ferroptosis have crosstalk via autophagy, potentially switch cell death under certain conditions. As two forms inflammatory programmed death, different effects on inflammation, cGAS-STING signaling pathway also involved. it plays important role progression some chronic diseases. This review discusses relationship between pyroptosis, attempts uncover reasons behind evasion nature

Language: Английский

Citations

2
Sodium citrate targeting Ca2+/CAMKK2 pathway exhibits anti-tumor activity through inducing apoptosis and ferroptosis in ovarian cancer DOI Creative Commons
Yulun Wu,

Chaoran Jia,

Wei Liu

et al.

Journal of Advanced Research, Journal Year: 2024, Volume and Issue: 65, P. 89 - 104

Published: May 7, 2024

Ovarian cancer (OC) is known for its high mortality rate. Although sodium citrate has anti-tumor effects in various cancers, effect and mechanism OC remain unclear. To analyze the inhibitory of on ovarian cells underlying mechanism. Cell apoptosis was examined by TUNEL staining, flow cytometry ferroptosis intracellular Fe2+, MDA, LPO assays respectively. metabolism OCR ECAR measurements. Immunoblotting immunoprecipitation were used to elucidate This study suggested that not only promoted cell but also triggered ferroptosis, manifested as elevated levels LPO, MDA lipid ROS production. On one hand, treatment led a decrease Ca2+ content cytosol chelating Ca2+, which further inhibited Ca2+/CAMKK2/AKT/mTOR signaling, thereby suppressing HIF1α-dependent glycolysis pathway inducing apoptosis. other chelation resulted inactivation CAMKK2 AMPK, leading increase NCOA4-mediated ferritinophagy, causing increased Fe2+ levels. More importantly, inhibition Ca2+/CAMKK2/AMPK signaling reduced activity MCU concentration within mitochondria, resulting an mitochondrial ROS. Additionally, metabolomic analysis indicated significantly de novo synthesis. Altogether, these factors contributed ferroptosis. As expected, supplementation successfully reversed death decreased tumor growth induced citrate. Inspiringly, it found coadministration sensitivity chemo-drugs. These results revealed exerted anti-cancer inhibiting Ca2+/CAMKK2-dependent Sodium will hopefully serve prospective compound improving efficacy

Language: Английский

Citations

11
HMGA2 alleviates ferroptosis by promoting GPX4 expression in pancreatic cancer cells DOI Creative Commons
Ziyang Luo, Qingfang Zheng, Shazhou Ye

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(3)

Published: March 16, 2024

Abstract Pancreatic cancer is one of the most malignant tumor types and characterized by high metastasis ability a low survival rate. As chromatin-binding protein, HMGA2 widely overexpressed considered an oncogene with various undefined regulatory mechanisms. Herein, we demonstrated that highly expressed in pancreatic tissues, mainly distributed epithelial cells, represents subtype epithelial–mesenchymal transition. Deletion inhibits malignancy through cell proliferation, metastasis, xenograft growth vivo. Moreover, enhanced cellular redox status inhibiting reactive oxygen species promoting glutathione production. Importantly, ferroptotic death was significantly ameliorated cells overexpressing HMGA2. Conversely, deletion exacerbated ferroptosis. Mechanistically, activated GPX4 expression transcriptional translational regulation. binds promotes cis-element modification promoter region gene enhancing enhancer activity increased H3K4 methylation H3K27 acetylation. Furthermore, stimulated protein synthesis via mTORC1-4EBP1 -S6K signaling axes. The overexpression alleviated decrease levels resulting from pharmacologic inhibition mTORC1. compared control, more strongly reduced phosphorylation 4EBP1 S6K. A strong positive correlation between confirmed using immunohistochemical staining. We also mitigated sensitivity to combination treatment ferroptosis inducer mTORC1 or gemcitabine. In summary, our results revealed mechanism which coordinates underscores potential value targeting treatment.

Language: Английский

Citations

8
Ferroptosis and cuproptosis: Metal-dependent cell death pathways activated in response to classical chemotherapy – Significance for cancer treatment? DOI Creative Commons
Mateusz Kciuk, Adrianna Gielecińska, Żaneta Kałuzińska‐Kołat

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2024, Volume and Issue: 1879(4), P. 189124 - 189124

Published: May 25, 2024

Apoptosis has traditionally been regarded as the desired cell death pathway activated by chemotherapeutic drugs due to its controlled and non-inflammatory nature. However, recent discoveries of alternative pathways have paved way for immune-stimulatory treatment approaches in cancer. Ferroptosis (dependent on iron) cuproptosis copper) hold promise selective cancer targeting overcoming drug resistance. Copper ionophores iron-bearing nano-drugs show potential clinical therapy single agents adjuvant treatments. Here we review up-to-date evidence involvement metal ion-dependent cytotoxicity classical (alkylating agents, topoisomerase inhibitors, antimetabolites, mitotic spindle inhibitors) their combinations with ferroptosis inducers, indicating prospects, advantages, obstacles use.

Language: Английский

Citations

8
Neuroscience of cancer: unraveling the complex interplay between the nervous system, the tumor and the tumor immune microenvironment DOI Creative Commons

Qibo Huang,

Bai Hu,

Zhang Ping

et al.

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 17, 2025

The study of the multifaceted interactions between neuroscience and cancer is an emerging field with significant implications for understanding tumor biology innovation in therapeutic approaches. Increasing evidence suggests that neurological functions are connected tumorigenesis. In particular, peripheral central nervous systems, synapse, neurotransmitters, neurotrophins affect progression metastasis through various regulatory approaches immune microenvironment. this review, we summarized tumorigenesis metastasis, which controlled by systems. We also explored roles neurotransmitters progression. Moreover, examined interplay system have identified drugs target treatment. review present work supporting agent targeting could potential to improve therapy.

Language: Английский

Citations

0
NGR‐Modified CAF‐Derived exos Targeting Tumor Vasculature to Induce Ferroptosis and Overcome Chemoresistance in Osteosarcoma DOI Creative Commons

Jianxin Du,

Xiangwei Meng, Minghao Yang

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 31, 2025

Osteosarcoma (OS) chemoresistance presents a significant clinical challenge. This study aims to investigate the potential of using tumor vascular-targeting peptide NGR-modified cancer-associated fibroblasts (CAFs)-derived exosomes (exos) deliver circ_0004872-encoded small peptides promoting autophagy-dependent ferroptosis reverse in OS. Through combined single-cell transcriptome analysis and high-throughput sequencing, it identified circ_0004872 associated with chemoresistance. Subsequent experiments demonstrated that encoded by this Circular RNA (circRNA) can effectively enhancing OS cell sensitivity chemotherapy via mechanism ferroptosis. Moreover, vitro vivo results confirmed efficient delivery CAFs-derived exo-packaged circ_0004872-109aa cells, thereby improving targeted therapy efficacy. not only offers novel strategy overcome but also highlights application value utilizing exos for drug delivery.

Language: Английский

Citations

0