Targeting ferroptosis for cancer therapy: exploring novel strategies from its mechanisms and role in cancers DOI Open Access
Minlin Jiang, Meng Qiao, Chuanliang Zhao

et al.

Translational Lung Cancer Research, Journal Year: 2020, Volume and Issue: 9(4), P. 1569 - 1584

Published: Aug. 1, 2020

Abstract: Ferroptosis is a novel form of non-apoptotic regulated cell death (RCD), with distinct characteristics and functions in physical conditions multiple diseases such as cancers. Unlike apoptosis autophagy, this new RCD an iron-dependent features lethal accumulation reactive oxygen species (ROS) over production lipid peroxidation. Excessive iron from aberrant metabolisms or the maladjustment two main redox systems thiols peroxidation role major causes ROS generation, redox-acrive ferrous (intracellular labile iron) crucial factor for Regulation ferrroptosis also involves different pathways mevalonate pathway, P53 pathway p62-Keap1-Nuclear (erythroid-derived 2)-like 2 (Nrf2) pathway. roles double-edged sword either suppressing promoting tumor progression release signaling molecules microenvironment. Emerging evidence suggests ferroptosis potential target cancer therapy inducers including small nanomaterials have been developed. The application relates to overcoming drug resistance preventing metastasis, may become promising strategy combined other anti-cancer therapies. Here, we summarize characters its underlying basis cancer, followed by possible applications therapies challenges maintained.

Language: Английский

Ferroptosis: a cell death connecting oxidative stress, inflammation and cardiovascular diseases DOI Creative Commons
Yi Yu, Yan Yuan,

Fanglin Niu

et al.

Cell Death Discovery, Journal Year: 2021, Volume and Issue: 7(1)

Published: July 26, 2021

Abstract Ferroptosis, a recently identified and iron-dependent cell death, differs from other death such as apoptosis, necroptosis, pyroptosis, autophagy-dependent death. This form of does not exhibit typical morphological biochemical characteristics, including shrinkage, mitochondrial fragmentation, nuclear condensation. The dysfunction lipid peroxide clearance, the presence redox-active iron well oxidation polyunsaturated fatty acid (PUFA)-containing phospholipids are three essential features ferroptosis. Iron metabolism peroxidation signaling increasingly recognized central mediators Ferroptosis plays an important role in regulation oxidative stress inflammatory responses. Accumulating evidence suggests that ferroptosis is implicated variety cardiovascular diseases atherosclerosis, stroke, ischemia-reperfusion injury, heart failure, indicating targeting will present novel therapeutic approach against diseases. Here, we provide overview features, process, function, mechanisms ferroptosis, its connected relevance to stress, inflammation,

Language: Английский

Citations

452
Ferroptosis in cancer and cancer immunotherapy DOI Creative Commons
Lei Zhao, Xiaoxue Zhou, Feng Xie

et al.

Cancer Communications, Journal Year: 2022, Volume and Issue: 42(2), P. 88 - 116

Published: Feb. 1, 2022

Abstract The hallmark of tumorigenesis is the successful circumvention cell death regulation for achieving unlimited replication and immortality. Ferroptosis a newly identified type dependent on lipid peroxidation which differs from classical programmed in terms morphology, physiology biochemistry. broad spectrum injury tumor tolerance are main reasons radiotherapy chemotherapy failure. effective rate immunotherapy as new treatment method less than 30%. can be seen radiotherapy, chemotherapy, immunotherapy; therefore, ferroptosis activation may potential strategy to overcome drug resistance mechanism traditional cancer treatments. In this review, characteristics causes by briefly described. addition, three metabolic regulations its crosstalk with signaling pathways summarized. Collectively, these findings suggest vital role based interaction immunotherapy, thus, indicating remarkable treatment.

Language: Английский

Citations

415
Inhibition of ferroptosis by up-regulating Nrf2 delayed the progression of diabetic nephropathy DOI
Shuangwen Li,

Lisi Zheng,

Jun Zhang

et al.

Free Radical Biology and Medicine, Journal Year: 2020, Volume and Issue: 162, P. 435 - 449

Published: Nov. 2, 2020

Language: Английский

Citations

299
Chondrocyte ferroptosis contribute to the progression of osteoarthritis DOI Creative Commons
Xudong Yao, Kai Sun, Shengnan Yu

et al.

Journal of Orthopaedic Translation, Journal Year: 2020, Volume and Issue: 27, P. 33 - 43

Published: Dec. 18, 2020

Osteoarthritis (OA) is a complex process comprised of mechanical load, inflammation, and metabolic factors. It still unknown that if chondrocytes undergo ferroptosis during OA contribute to the progression OA. In our study, we use Interleukin-1 Beta (IL-1β) simulate inflammation ferric ammonium citrate (FAC) iron overload in vitro. Also, used surgery-induced destabilized medial meniscus (DMM) mouse model induce vivo. We verify by its definition defined Nomenclature Committee on Cell Death with both vitro vivo model. observed IL-1β FAC induced reactive oxygen species (ROS), lipid ROS accumulation related protein expression changes chondrocytes. Ferrostatin-1, specific inhibitor, attenuated cytotoxicity, lipid-ROS facilitated activation Nrf2 antioxidant system. Moreover, erastin, most classic inducer ferroptosis, promoted matrix metalloproteinase 13 (MMP13) while inhibited type II collagen (collagen II) At last, proved intraarticular injection ferrostatin-1 rescued cartilage degradation mice summary, study firstly underwent under condition. Induction caused increased MMP13 decreased Furthermore, inhibition ferrostatin-1, case, seems be novel promising option for prevention The translation potential this article first indicated chondrocyte osteoarthritis which provides strategy

Language: Английский

Citations

291
Statins: a repurposed drug to fight cancer DOI Creative Commons
Wen Jiang,

Jin-Wei Hu,

Xu-Ran He

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2021, Volume and Issue: 40(1)

Published: July 24, 2021

As competitive HMG-CoA reductase (HMGCR) inhibitors, statins not only reduce cholesterol and improve cardiovascular risk, but also exhibit pleiotropic effects that are independent of their lipid-lowering effects. Among them, the anti-cancer properties have attracted much attention indicated potential as repurposed drugs for treatment cancer. A large number clinical epidemiological studies described anticancer statins, evidence effectiveness is inconsistent. It may be certain molecular subtypes cancer more vulnerable to statin therapy than others. Whether still an active area research. Statins appear enhance efficacy address shortcomings associated with conventional treatments, suggesting should considered in context combined therapies Here, we present a comprehensive review treatments. We discuss current understanding mechanisms underlying on different malignancies. provide recommendations design future well-designed trials statins.

Language: Английский

Citations

265
Ferroptosis and its emerging roles in cardiovascular diseases DOI
Ning Li, Wenyang Jiang, Wei Wang

et al.

Pharmacological Research, Journal Year: 2021, Volume and Issue: 166, P. 105466 - 105466

Published: Feb. 5, 2021

Language: Английский

Citations

196
Baicalin induces ferroptosis in bladder cancer cells by downregulating FTH1 DOI Creative Commons
Na Kong, Xiaying Chen, Jiao Feng

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2021, Volume and Issue: 11(12), P. 4045 - 4054

Published: March 27, 2021

Ferroptosis is a non-apoptotic regulated cell death caused by iron accumulation and subsequent lipid peroxidation. Currently, the therapeutic role of ferroptosis on cancer gaining increasing interest. Baicalin an active component in

Language: Английский

Citations

193
Verification of ferroptosis and pyroptosis and identification of PTGS2 as the hub gene in human coronary artery atherosclerosis DOI

Yaqing Zhou,

Hanxiao Zhou, Lei Hua

et al.

Free Radical Biology and Medicine, Journal Year: 2021, Volume and Issue: 171, P. 55 - 68

Published: May 8, 2021

Language: Английский

Citations

179
Molecular mechanisms of ferroptosis and their involvement in brain diseases DOI Creative Commons
Inês Costa, Daniel José Barbosa, Sofia Benfeito

et al.

Pharmacology & Therapeutics, Journal Year: 2023, Volume and Issue: 244, P. 108373 - 108373

Published: March 8, 2023

Ferroptosis is a type of regulated cell death characterized by intracellular accumulation iron and reactive oxygen species, inhibition system Xc-, glutathione depletion, nicotinamide adenine dinucleotide phosphate oxidation lipid peroxidation. Since its discovery characterization in 2012, many efforts have been made to reveal the underlying mechanisms, modulating compounds, involvement disease pathways. inducers include erastin, sorafenib, sulfasalazine glutamate, which, inhibiting prevent import cysteine into cells. RSL3, statins, Ml162 Ml210 induce ferroptosis peroxidase 4 (GPX4), which responsible for preventing formation peroxides, FIN56 withaferin trigger GPX4 degradation. On other side, inhibitors ferrostatin-1, liproxstatin-1, α-tocopherol, zileuton, FSP1, CoQ10 BH4, interrupt peroxidation cascade. Additionally, deferoxamine, deferiprone N-acetylcysteine, targeting cellular pathways, also classified as inhibitors. Increased evidence has established distinct brain diseases, including Alzheimer's, Parkinson's Huntington's amyotrophic lateral sclerosis, multiple Friedreich's ataxia. Thus, deep understanding how contributes these it can be modulated, open new window opportunities novel therapeutic strategies targets. Other studies shown sensitivity cancer cells with mutated RAS induction that chemotherapeutic agents synergize tumor treatment. tempting consider may arise target mechanistic pathway treatment tumors. Therefore, this work provides an up-to-date review on molecular mechanisms their diseases. In addition, information main targets provided.

Language: Английский

Citations

174
Liproxstatin-1 attenuates unilateral ureteral obstruction-induced renal fibrosis by inhibiting renal tubular epithelial cells ferroptosis DOI Creative Commons
Bo Zhang, Xiang Chen, Ru Feng

et al.

Cell Death and Disease, Journal Year: 2021, Volume and Issue: 12(9)

Published: Sept. 11, 2021

Abstract Renal fibrosis is a common pathological process that occurs with diverse etiologies in chronic kidney disease. However, its regulatory mechanisms have not yet been fully elucidated. Ferroptosis form of non-apoptotic regulated cell death driven by iron-dependent lipid peroxidation. It currently unknown whether ferroptosis initiated during unilateral ureteral obstruction (UUO)-induced renal and role has determined. In this study, we demonstrated induced tubular epithelial cells (TECs) vivo. The inhibitor liproxstatin-1 (Lip-1) reduced iron deposition, death, peroxidation, inhibited the downregulation GPX4 expression UUO, ultimately inhibiting TECs. We found Lip-1 significantly attenuated UUO-induced morphological changes collagen deposition mice. addition, profibrotic factors UUO model. vitro, used RSL3 treatment knocked down level RNAi HK2 to induce ferroptosis. Our results indicated secreted various was able inhibit thereby secretion process. Incubation fibroblasts culture medium from RSL3-induced promoted fibroblast proliferation activation, whereas impeded effects. study may relieve Mechanistically, could reduce activation surrounding paracrine cells. potentially be as therapeutic approach for fibrosis.

Language: Английский

Citations

137