Ferroptosis: Emerging Role in Diseases and Potential Implication of Bioactive Compounds
Abstract
:1. Introduction
2. Ferroptosis: An Overview
3. Mechanism of Ferroptosis
3.1. Iron Homeostasis
3.2. Lipid Metabolism
3.3. Antioxidant Defense Systems
Erythroid Nuclear Factor 2-Related Factor and p53
4. Ferroptosis Implication in Diseases
4.1. Cancer
4.2. Neurological Diseases
4.2.1. Alzheimer’s Disease
4.2.2. Parkinson’s Disease
4.2.3. Huntington’s Disease
4.2.4. Amyotrophic Lateral Sclerosis
4.3. Cardiovascular Diseases
4.4. Ischemic Reperfusion Injury
5. Ferroptosis Modulators
6. Natural Ferroptosis Regulators
6.1. Natural Inducers
6.2. Natural Inhibitors
Polyphenols
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
References
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Ferroptosis | Necroptosis | Apotosis | Autophagy | Pyroptosis | References | |
---|---|---|---|---|---|---|
Cell morphology | Swelling, reduction of mithocondrial cristae | Swelling | Shrinkage, intercellular junction disappearence | Vescicles in cytoplasm, autophagosome formation | Swelling, bubbling | [1,2,4] |
Membrane | — | Rupture plasma membrane | Membrane blebbing | — | Rupture plasma membrane | [1,4] |
Nucleus | — | Pyknosis, Karyorrhexis, Karyolysis | Chromatine condensation and nuclear disintegration | Chromatine condensation | [1,4] | |
Biochemical features | Iron and ROS accumulation, GSH depletion, lipid peroxidation | Lower ATP level | Caspase 3, 6, 7 activation | Caspase 1, 4, 5, 11 activation | [1,2,4] |
Drugs | Nature of the Compound | Targets | Test Models | Functions | References |
---|---|---|---|---|---|
Deferoxamine | Synthetic | Iron | HT-1080; Calu-1; BJeLR; PC12; MEF cells; Aging model mice | Iron chelation; ROS generation inhibition; Lipid peroxidation inhibition | [2,17,152,155] |
Deferiprone (DFP) | Synthetic | Iron | Patients with iron overload | Iron chelation; ROS generation inhibition | [153] |
Ferrostatin-1 | Synthetic | 15-LOX/PEBP1 | HT-1080 cells | Free radical scavenger; Lipid peroxidation inhibition | [158,159] |
Lipro-1 | Synthetic | — | OLN-93 cell line | Lipid peroxidation inhibition; GPx4 expression improved; GSH levels increase | [145,159,160] |
Glycyrrhizin (GLY) | Natural | HMGB1/GPx4 Pathway | Hepatocytes | Lipid peroxidation inhibition | [173,174,175] |
Cryptotanshinone | Natural | STAT3 | PDAC cell lines | Silencing STAT3 | [133] |
N-acetylcysteine | Natural | JAK-STAT pathway | ICH model mice and rats | GSH increase; ROS generation inhibition; Lipid peroxidation inhibition | [75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127,128,129,130,131,132,133,134,135,136,137,138,139,140,141,142,143,144,145,146,147,148,149,150,151,152,153,154,155,156,157,158,159,160,161,162,163,164,165,166,167,168,169,170,171,172,173,174,175,176] |
Curcumin | Natural | Iron | Mouse models; Mouse insulinoma pancreatic cells (MIN6) | GPx4 increased expression; Lipid peroxidation inhibition; Iron chelation | [179,180,181,182] |
Epigallocatechin gallate (EGCG) | Natural | Iron | Mouse insulinoma pancreatic cells (MIN6) | Iron chelation; Lipid peroxidation inhibition | [181,182,183] |
Apigenin | Natural | GPx4; SIRT1 | Human neuroblastoma SH-SY5Y cells | ROS generation inhibition; GPx4 and SIRT1 induction | [184] |
Quercetin | Natural | Iron | Mouse cells | Lipid peroxidation inhibition; Iron chelation | [185,186,187] |
Baicalein | Natural | GPx4; Nrf2 | Human pancreatic cancer cells (BxPc3); Epithelioid carcinoma cells (PANC1) | ROS generation inhibition; Lipid peroxidation inhibition | [188] |
Drugs | Nature of the Compound | Targets | Test Models | Functions | References |
---|---|---|---|---|---|
RSL-3 | Synthetic | GPx4 | Cancer cells | GPx4 inhibition; ROS generation inhibition | [137,138,139] |
Erastin | Synthetic | System Xc−; VDAC2; | Cancer cells | VDAC2 inhibition; System Xc− inhibition; GSH reduction | [140,141,142,143,144,145] |
FIN56 | Synthetic | GPx4 | Cancer cells | GPx4 depletion; Squalene synthase activation | [146,147,148,149,150] |
Artemisinin | Natural | Iron | Cancer cells | ROS generation Lipid peroxidation increase | [2,164,165,166] |
Isothiocyanates (ITCs) | Natural | Iron MAPK signaling pathway | Cancer cells | ROS generation | [167,168,169] |
Gambogic acid (GA) | Natural | Thioredoxin system | Cancer cells | ROS generation | [170,171,172,173] |
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Patanè, G.T.; Putaggio, S.; Tellone, E.; Barreca, D.; Ficarra, S.; Maffei, C.; Calderaro, A.; Laganà, G. Ferroptosis: Emerging Role in Diseases and Potential Implication of Bioactive Compounds. Int. J. Mol. Sci. 2023, 24, 17279. https://doi.org/10.3390/ijms242417279
Patanè GT, Putaggio S, Tellone E, Barreca D, Ficarra S, Maffei C, Calderaro A, Laganà G. Ferroptosis: Emerging Role in Diseases and Potential Implication of Bioactive Compounds. International Journal of Molecular Sciences. 2023; 24(24):17279. https://doi.org/10.3390/ijms242417279
Chicago/Turabian StylePatanè, Giuseppe Tancredi, Stefano Putaggio, Ester Tellone, Davide Barreca, Silvana Ficarra, Carlo Maffei, Antonella Calderaro, and Giuseppina Laganà. 2023. "Ferroptosis: Emerging Role in Diseases and Potential Implication of Bioactive Compounds" International Journal of Molecular Sciences 24, no. 24: 17279. https://doi.org/10.3390/ijms242417279