IMR Press / FBL / Volume 25 / Issue 6 / DOI: 10.2741/4848
Open Access Review
Instrumental role for reactive oxygen species in the inflammatory response
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1 Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada
2 Departments of Pathology, Microbiology and Immunology, and Surgery, Dalhousie University, Halifax, Nova Scotia, Canada
Front. Biosci. (Landmark Ed) 2020, 25(6), 1110–1119;
Published: 1 March 2020
(This article belongs to the Special Issue Pro and con iron and ROS in inflammation and infection)

Because of their highly reactive nature and potentially toxic characteristic, reactive oxygen species (ROS) have had a bad reputation for years. However, under certain conditions, ROS generation has shown positive outcomes. It is ROS imbalance that causes toxic effects. ROS play an important role in physiological processes such as cell signaling, senescence, inflammation, and the immune response to infection. An increasing number of studies highlight the importance of ROS for the inflammatory response, whether sterile or due to infection or cancer. The purpose of this paper is to present evidence of the essential role of ROS in the inflammatory response.

Reactive Oxygen Species

Free radicals are unstable and highly reactive atoms or molecules due to unpaired electrons in their outermost shell. In order to pair these electrons and become stable, free radicals tend to "attack" the nearest stable molecules by redox reactions. Because most reactive oxygen species (ROS) are free radicals, these two terms are often used in an interchangeable fashion. However, free radicals also include reactive nitrogen species (e.g., nitric oxide - NO·), reactive lipid species (e.g., lipid alkoxyl - LO·, lipid peroxyl - LOO·). In addition, ROS include other molecules such as hydrogen peroxide (H2O2) that are not free radicals. This review will focus on ROS.

ROS are naturally produced in aerobic species, in which mitochondria are the main source of free radicals. ROS are produced during cellular respiration, a vital function that generates energy for the metabolism of the cells. The process starts in the cytoplasm with the conversion of glucose into pyruvate, which is then oxidized in the mitochondrial matrix and will produce nicotinamide adenine dinucleotide (NADH, electron transporter), flavin adenine dinucleotide (FADH2, electron transporter) and adenosine triphosphate (ATP, energy). The NADH and FADH2 previously produced, and the electrons that they transport, move to the electron transport chain located in the mitochondrial inner membrane. The electron transport chain is formed by four complexes: complex I or NADH dehydrogenase, complex II or succinate-ubiquinone oxidoreductase, complex III or cytochrome c reductase, and complex IV or cytochrome c oxidase (1). The electrons are transmitted to these 4 complexes which eject protons, leading to a membrane potential across the mitochondria that triggers ATP synthesis by ATP-synthase. During electron transport, complexes I and III generate O2·−. The produced O2·− can then be converted: first into H2O2 by superoxide dismutase 2 (SOD2); second, O2·− leads to the highly reactive HO· (hydroxyl radical) through the Fenton reaction in the presence of free iron; and third, the O2·− can also react with NO· to form the highly reactive peroxynitrite (ONOO·) molecule. Mitochondrial ROS is released as a result of oxidative stress-induced opening of the mitochondrial permeability transition pore (MPTP). ROS can also be generated by other sources, including the endoplasmic reticulum, peroxisome, prostaglandin synthesis and cytochrome P450 (2). ROS, which are very unstable and hyper-reactive molecules, are produced continuously in living beings; hence, to maintain redox homeostasis and avoid undesirable damaging effects, ROS levels are controlled by antioxidants (e.g., superoxide dismutase, glutathione and catalases; vitamins A, E and C).

For a very long time, ROS were considered to be detrimental, dangerous, toxic or even deadly molecules. Therefore, the goal of many studies was to identify strategies to reduce the production of cellular ROS and/or increase the level of antioxidants within cells (3–7). However, it is increasingly apparent that ROS are important signaling molecules, as well as mediators of inflammation. ROS play a critical role in physiological processes such as cell growth and signaling, senescence, differentiation, inflammation, apoptosis, and the immune response to infection (1, 8). During inflammation, ROS production increases to participate in the resolution of inflammation and promotion of wound healing. This increase is the result of an incompletely known process involving alteration of iron homeostasis, stimulation of the nuclear factor-kappa B transcription factor (NF-κB) and the reduction of certain antioxidants. The purpose of this review is to highlight how essential ROS are throughout the inflammatory response. We will focus on the role of ROS in clearance of damaged or infected cells, and cancer development.


ROS have a beneficial role in sterile inflammation (i.e., inflammation without pathogens), which is triggered by cellular damage under conditions such as ischemia-reperfusion injury, exposure to toxins, and arthritis (9, 10). During sterile inflammation, ROS are involved in the clearance of damaged cells, as well as in the differentiation of macrophages (11–13).

To maintain homeostasis, damaged, stressed or dying cells trigger specific mechanisms that result in their elimination. In the absence of those mechanisms, cell death occurs via necrosis, while in the presence of regulation cell death is described as apoptosis or autophagy (14, 15). Dying cells express molecules that act as danger signals in order to attract phagocytic cells (e.g. macrophages) that phagocytose and eliminate the cell. This process happens in 3 main stages (16): stage 1, expression by dying cells of “find me” signals that attract macrophages; stage 2, expression of “eat me” signals that stimulate macrophages to engulf the cell, and the disintegration of “do not eat me” signals that would otherwise prevent macrophages from attacking host cells; finally, stage 3, the engulfment of damaged or dying cells by the macrophage. ROS play an important role in all of these stages. Dying cells expose their components to the extracellular environment as a damaging-associated molecular pattern (DAMPs) in order to activate macrophages. DAMPs are cellular components - such as high-mobility group box 1 (HMGB1), mitochondrial DNA, ATP, uric acid, and many others - that are externalized (17), and recognized by pattern recognition receptors (PRRs) of phagocytic cells. Pattern recognition receptors include Toll-like receptors (TLRs), NOD receptors (NLRs) and RIG-I receptors (RLRs) (18). Despite the fact that the relationship between ROS and DAMPs remains incompletely understood, it seems that ROS play a key role in this stage since DAMPs must be oxidized prior to being externalized as danger signals. Studies by Chang et al. (19, 20) corroborated the idea by using mouse monoclonal antibodies to block oxidized low-density lipoprotein (OxLDL), a molecule that competes with DAMPs to bind to macrophages. Chang et al. found that these antibodies bind efficiently to OxLDL, but also bind to DAMPs of apoptotic cells and prevent phagocytosis of target cells by peritoneal macrophages. The results of these studies strongly suggest that DAMPs can be oxidized (21, 22). Studies show the importance of ROS for the recognition and the engulfment of damaged cells (12, 23). The last step in the clearance of damaged cells is phagocytosis. ROS are essential for dying cells (apoptotic and necrotic) that need to be phagocytized. After engulfing damaged cells, macrophages initiate a respiratory burst, i.e., the quick increase in intracellular ROS that gradually degrades damaged cells (Figure 1). The process begins by an increase in oxygen (O2) uptake by phagocytes. Then a considerable amount of ROS is produced by the conversion of O2 to superoxide followed by the conversion of superoxide into hydrogen peroxide, respectively, by the enzymes NADPH oxidase and superoxide dismutase. Hydrogen peroxide and superoxide damage the engulfed molecules but mainly participate in the production of a third molecule called hypochlorite (HOCl) by the effect of the myeloperoxidase on hydrogen peroxide (24). ROS are also critical to trigger autophagy or "self-eating", which is a mechanism by which a cell engulfs and breaks down its own components in the lysosome and recycles them for new biosynthesis (23).

Figure 1

. Respiratory burst in phagocytic cells. Phagocytic cells (neutrophils, macrophages, etc.) are able to initiate respiratory burst to gradually degrade engulfed elements such as bacteria or damaged cells. The process starts by an increase in oxygen (O2) uptake by phagocytes. The oxygen is converted in superoxide (O2·−) by the enzyme NADPH oxidase. Some superoxide can already damage the engulfed particle but undergo another reaction by the superoxide dismutase to produce hydrogen peroxide (H2O2). This last molecule is converted in hypochlorite (HOCl) by the myeloperoxidase.

As previously mentioned, phagocytic cells such as macrophages are important in inflammation. Two types of macrophages have been described. The first type are the classical activated macrophages, designated M1 macrophages. They have a strong microbicidal function and are able to secrete large amounts of proinflammatory molecules. The second type of macrophages are the alternative activated macrophages, designated M2 macrophages, that are involved in wound healing and tissue repair, and produce high levels of anti-inflammatory mediators (25). The process by which macrophage differentiation occurs is complex and not yet fully understood; nevertheless, studies have shown that ROS are instrumental in this process (10, 12, 26, 27). Zhang et al. found that ROS are produced during macrophage differentiation and that the use of butylated hydroxyanisole or other ROS inhibitors blocks the process (26). It seems that a "high level" of ROS leads to the differentiation of M2 macrophages while a “low level” of ROS results in M1 macrophages since only the development of M2 macrophages is compromised when ROS are inhibited.

In summary, ROS play a critical role in the immune response to sterile inflammation by participating in the differentiation of macrophages, promoting macrophage attraction by damaged cells, and contributing to the phagocytic process by aiding in the degradation of engulfed cells. Blocking or inhibiting ROS compromises these natural processes. ROS are also useful during the inflammatory response to foreign agents (such as bacteria, viruses, fungi, and parasites,) that are not normally present within the body.


The process by which the body eliminates foreign invaders and the cells that these invaders have infected is similar to sterile inflammation, in that ROS play a critical role in this process as they actively participate in the elimination of pathogens (28). When pathogenic microbes invade the body, they activate vascular endothelial cells, which then produce chemoattractants and express adhesion molecules to promote recruitment and migration of leukocytes to the site of infection. Pathogens possess specific molecular motifs called pathogen-associated molecular pattern (PAMPs) that are recognized by the PRRs of phagocytes (29). The eradication of pathogens by phagocytosis in a fashion similar to the one described in sterile inflammation then occurs, in which pathogens are engulfed by phagocytes and the subsequent respiratory burst leads to their disintegration. The detailed process by which ROS seems to lead to the death of pathogens is still not fully understood, yet a study suggest that ROS can damage pathogens by reacting directly or indirectly with key components of microbes (30). ROS can alter the DNA, RNA, proteins and lipids of pathogens or change the microenvironment surrounding the foreign invader in order to stimulate enzymes called proteases that can break down proteins (31).

Another mechanism by which ROS cause the death of microbes is NETosis. This is the ultimate defense system of neutrophils. When the number of pathogens is very high and/or pathogens are very large and therefore difficult to phagocytose, neutrophils are able to condense their chromatin and eject their DNA and antimicrobial agents in the direction of pathogens. These structures are called neutrophil extracellular traps (NETs) and the process by which they are produced is called NETosis (32, 33). The purpose of the NETosis is to provide elevated concentration of antimicrobial components and also physically snare pathogens. The entire process begins with the recognition of PAMPs by neutrophil PPRs, followed by activation of a Raf / MEK / ERK kinase pathway responsible for activation of the NADPH complex and production of ROS that seems to be the leading cause of chromatin condensation, as well as neutrophil plasma membrane degradation followed by extracellular DNA release with antimicrobial agents to trap microbes (34). However, in situations where the immune system is overactivated and the cellular respiration impaired, the redox equilibrium is broken, causing a considerable rise in the levels of intracellular ROS. Such a situation may result in damage to the host, including the death of surrounding healthy cells, damage to the vascular system, multiorgan dysfunction and even death (35–37).


It has been suggested that excessive ROS produced by immune cells during inflammation may lead to genetic mutations that can trigger carcinogenesis (38). The relationship between ROS and cancer cells is ambiguous; whereas, certain levels of ROS seem to promote carcinogenesis, high ROS levels can also eradicate cancer cells by triggering death pathways (39, 40). Different types of cancers (e.g., breast, pancreas, bladder, colon) generate ROS to promote growth, angiogenesis, chemoresistance and the ability to invade other organs or tissues (41). At the same time, cancer cells also express high concentrations of antioxidants to prevent triggering death pathways, i.e., necrosis, apoptosis or autophagy (Figure 2). Therefore, targeting the balance that exists between ROS production and antioxidant production represents a potential target for cancer treatment.

Figure 2

(40): Cellular effect of ROS increase and antioxidant balance. A balance between ROS (reactive oxygen species) and antioxidant defense (AOD) is very important for healthy cells. An increase in oxidative pressure engenders upregulation of antioxidant to prevent cancerogenesis. An imbalance between ROS and antioxidants can promote the development and survival of cancer. Cancer cells tip the scales in favor of the ROS to maintain their increased metabolic activity. At the same time, to prevent ROS from reaching threshold that trigger cell death mechanisms, cancer cells increase antioxidant levels. When ROS level increase further (physiologically or therapeutically for example), the growth of cancer cells slow down then death pathways like necrosis, apoptosis or autophagy are trigger.

Upadhyaya et al. showed that the nontoxic dietetic component phenethyl isothiocyanate (PEITC) promotes the reduction of the antioxidant glutathione, leading to suppression of proliferation and early apoptosis of cancer cells due to a rise in intracellular ROS levels (42). Another study by Chen et al. suggested that the ROS inducer EF24 improves the efficacy of anti-neoplastic chemotherapy with rapamycin in human gastric cancer cells in vitro and in mouse models of cancer in vivo (43). Other studies have shown similar anti-neoplastic effects of PEITC and EF24 on different types of cancer cells (44–47).

Whereas strategies to induce excessive ROS production seem to be promising overall as a therapeutic approach against cancer, the potential benefits of ROS inhibition in carcinogenesis are controversial and less well studied. On one hand, molecules with antioxidative properties such as vitamin C and N-acetylcysteine show inhibitory effects on cancer progression, but on the other hand, these same molecules plus vitamin E and beta-carotene increase the rate of cancer development under certain conditions (48). The effect of antioxidants appears to be dependent on the stage of carcinogenesis (49). Early during the carcinogenesis, antioxidant expression by cancer cells is reduced because high levels of ROS are required to induce and maintain genetic mutations. Later on, cancer cells produce high levels of antioxidants in order to prevent intracellular ROS from reaching a cytotoxic level (40). Therefore, administration of antioxidants in the early stages of cancer development should most likely be protective whereas at a later stage, antioxidant could promote cancer progression.


There is an increasing body of evidence that ROS are beneficial under certain pathological conditions. During inflammation, ROS participate in cell signaling and the elimination of damaged or infected cells. ROS oxidize PAMPs and DAMPs to allow the phagocytes to recognize and eliminate these cells. ROS also regulate the process of phagocytosis, from the engulfment to the digestion of foreign particles and pathogens. The role of ROS in cancer is complex. On one hand, ROS can promote carcinogenesis but, on the other hand, ROS are promising targets for cancer treatment. The duality of ROS-related harm and benefits highlights the importance of maintaining homeostatic ROS production by eukaryotic cells.


This work received no external funding. The authors declare no conflict of interest.


adenosine triphosphate


damaging-associated molecular pattern


flavin adenine dinucleotide 2


hydrogen peroxide


high-mobility group box 1




lipid alkoxyl


lipid peroxyl


mitochondrial permeability transition pore


nicotinamide adenine dinucleotide


nuclear factor-kappa B transcription factor


NOD like receptors


nitric oxide




oxidized low-density lipoprotein


pathogen-associated molecular pattern


phenethyl isothiocyanate


pattern recognition receptors


RIG-I like receptors


reactive oxygen species


superoxide dismutase 2


Toll-like receptors

MittalMSiddiquiMRTranKReddySPMalikABReactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal201420112667DOI: 10.1089/ars.2012.5149 PMid:23991888 PMCid:PMC3929010
MeoS DiReedTTVendittiPVictorVMRole of ROS and RNS Sources in Physiological and Pathological Conditions. Oxid Med Cell Longev201620161245049DOI: 10.1155/2016/1245049 PMid:27478531 PMCid:PMC4960346
ChangH-CWuRShangMSatoTChenCShapiroJSLiuTThakurASawickiKTPrasadSVNArdehaliHReduction in mitochondrial iron alleviates cardiac damage during injury. EMBO Mol Med2016824767DOI: 10.15252/emmm.201505748 PMid:26896449 PMCid:PMC4772952
GrangerDNKvietysPRReperfusion injury and reactive oxygen species: The evolution of a concept. Redox Biol2015652451DOI: 10.1016/j.redox.2015.08.020 PMid:26484802 PMCid:PMC4625011
ChoiJHChoiAYYoonHChoeWYoonK-SHaJYeoE-JKangIBaicalein protects HT22 murine hippocampal neuronal cells against endoplasmic reticulum stress-induced apoptosis through inhibition of reactive oxygen species production and CHOP induction. Exp Mol Med20104281122DOI: 10.3858/emm.2010.42.12.084 PMid:20959717 PMCid:PMC3015155
OlyaeeMSontagSSalmanWSchnellTMobarhanSEiznhamerDKeshavarzianAMucosal reactive oxygen species production in oesophagitis and Barrett's oesophagus. Gut19953716873DOI: 10.1136/gut.37.2.168 PMid:7557561 PMCid:PMC1382711
TafaniMSansoneLLimanaFArcangeliTSantisE DePoleseMFiniMRussoMAThe Interplay of Reactive Oxygen Species, Hypoxia, Inflammation, and Sirtuins in Cancer Initiation and Progression. Oxid Med Cell Longev20162016118DOI: 10.1155/2016/3907147 PMid:26798421 PMCid:PMC4699039
Redza-DutordoirMAverill-BatesDAActivation of apoptosis signalling pathways by reactive oxygen species. Biochim Biophys Acta - Mol Cell Res2016186329772992DOI: 10.1016/j.bbamcr.2016.09.012 PMid:27646922
ShenHKreiselDGoldsteinDRProcesses of sterile inflammation. J Immunol2013191285763DOI: 10.4049/jimmunol.1301539 PMid:24014880 PMCid:PMC3787118
ChenYZhouZMinWMitochondria, Oxidative Stress and Innate Immunity. Front Physiol201891487DOI: 10.3389/fphys.2018.01487 PMid:30405440 PMCid:PMC6200916
DavalliPMiticTCaporaliALauriolaAD'ArcaDROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age-Related Diseases. Oxid Med Cell Longev201620163565127DOI: 10.1155/2016/3565127 PMid:27247702 PMCid:PMC4877482
TanH-YWangNLiSHongMWangXFengYThe Reactive Oxygen Species in Macrophage Polarization: Reflecting Its Dual Role in Progression and Treatment of Human Diseases. Oxid Med Cell Longev201620162795090DOI: 10.1155/2016/2795090 PMid:27143992 PMCid:PMC4837277
YangWTaoYWuYZhaoXYeWZhaoDFuLTianCYangJHeFTangLNeutrophils promote the development of reparative macrophages mediated by ROS to orchestrate liver repair. Nat Commun2019101076DOI: 10.1038/s41467-019-09046-8 PMid:30842418 PMCid:PMC6403250
KryskoD VBergheT VandenD'HerdeKVandenabeelePApoptosis and necrosis: Detection, discrimination and phagocytosis. Methods200844205221DOI: 10.1016/j.ymeth.2007.12.001 PMid:18314051
FilomeniGZioD DeCecconiFOxidative stress and autophagy: the clash between damage and metabolic needs. Cell Death Differ201522377388DOI: 10.1038/cdd.2014.150 PMid:25257172 PMCid:PMC4326572
BrüneBDehneNGrossmannNJungMNamgaladzeDSchmidTKnethenA vonWeigertARedox control of inflammation in macrophages. Antioxid Redox Signal201319595637DOI: 10.1089/ars.2012.4785 PMid:23311665 PMCid:PMC3718318
VénéreauECeriottiCBianchiMEDAMPs from Cell Death to New Life. Front Immunol20156422DOI: 10.3389/fimmu.2015.00422 PMid:26347745 PMCid:PMC4539554
RubartelliALotzeMTInside, outside, upside down: damage-associated molecular-pattern molecules (DAMPs) and redox. Trends Immunol200728429436DOI: 10.1016/ PMid:17845865
ChangMKBergmarkCLaurilaAHörkköSHanKHFriedmanPDennisEAWitztumJLMonoclonal antibodies against oxidized low-density lipoprotein bind to apoptotic cells and inhibit their phagocytosis by elicited macrophages: evidence that oxidation-specific epitopes mediate macrophage recognition. Proc Natl Acad Sci U S A19999663538DOI: 10.1073/pnas.96.11.6353 PMid:10339591 PMCid:PMC26885
ChangM-KBinderCJTorzewskiMWitztumJLC-reactive protein binds to both oxidized LDL and apoptotic cells through recognition of a common ligand: Phosphorylcholine of oxidized phospholipids. Proc Natl Acad Sci2002991304313048DOI: 10.1073/pnas.192399699 PMid:12244213 PMCid:PMC130583
TyurinVABalasubramanianKWinnicaDTyurinaYYVikulinaASHeRRKapralovAAMacpheeCHKaganVEOxidatively modified phosphatidylserines on the surface of apoptotic cells are essential phagocytic 'eat-me' signals: cleavage and inhibition of phagocytosis by Lp-PLA2. Cell Death Differ201421825835DOI: 10.1038/cdd.2014.1 PMid:24464221 PMCid:PMC3978307
KaganVEBorisenkoGGSerinkanBFTyurinaYYTyurinVAJiangJLiuSXShvedovaAAFabisiakJPUthaisangWFadeelBAppetizing rancidity of apoptotic cells for macrophages: oxidation, externalization, and recognition of phosphatidylserine. Am J Physiol Cell Mol Physiol2003285L1L17DOI: 10.1152/ajplung.00365.2002 PMid:12788785
SenaLAChandelNSPhysiological roles of mitochondrial reactive oxygen species,2012DOI: 10.1016/j.molcel.2012.09.025 PMid:23102266 PMCid:PMC3484374
ThomasDCThe phagocyte respiratory burst: Historical perspectives and recent advances. Immunol Lett20171928896DOI: 10.1016/j.imlet.2017.08.016 PMid:28864335
CovarrubiasABylesVHorngTROS sets the stage for macrophage differentiation. Cell Res2013239845DOI: 10.1038/cr.2013.88 PMid:23835480 PMCid:PMC3731567
ZhangYChoksiSChenKPobezinskayaYLinnoilaILiuZ-GROS play a critical role in the differentiation of alternatively activated macrophages and the occurrence of tumor-associated macrophages. Cell Res201323898914DOI: 10.1038/cr.2013.75 PMid:23752925 PMCid:PMC3698641
XuQChoksiSQuJJangJChoeMBanfiBEngelhardtJFLiuZNADPH Oxidases Are Essential for Macrophage Differentiation. J Biol Chem20162912003020041DOI: 10.1074/jbc. M116.731216 PMid:27489105 PMCid:PMC5025689
RahalAKumarASinghVYadavBTiwariRChakrabortySDhamaKOxidative stress, prooxidants, and antioxidants: the interplay. Biomed Res Int20142014761264DOI: 10.1155/2014/761264 PMid:24587990 PMCid:PMC3920909
SantoniGCardinaliCMorelliMSantoniMNabissiMAmantiniCDanger- and pathogen-associated molecular patterns recognition by pattern-recognition receptors and ion channels of the transient receptor potential family triggers the inflammasome activation in immune cells and sensory neurons. J Neuroinflammation20151221DOI: 10.1186/s12974-015-0239-2 PMid:25644504 PMCid:PMC4322456
HongYLiLLuanGDrlicaKZhaoXContribution of reactive oxygen species to thymineless death in Escherichia coli. Nat Microbiol2017216671675DOI: 10.1038/s41564-017-0037-y PMid:28970486 PMCid:PMC5705385
PaivaCNBozzaMTAre Reactive Oxygen Species Always Detrimental to Pathogens? Antioxid Redox Signal20142010001037DOI: 10.1089/ars.2013.5447 PMid:23992156 PMCid:PMC3924804
RemijsenQKuijpersTWWirawanELippensSVandenabeelePBergheT VandenDying for a cause: NETosis, mechanisms behind an antimicrobial cell death modality. Cell Death Differ201118581588DOI: 10.1038/cdd.2011.1 PMid:21293492 PMCid:PMC3131909
MesaMANETosisG VasquezAutoimmune Dis20132013651497DOI: 10.1155/2013/651497 PMid:23476749 PMCid:PMC3576733
Delgado-RizoVMartínez-GuzmánMAIñiguez-GutierrezLGarcía-OrozcoAAlvarado-NavarroAFafutis-MorrisMNeutrophil Extracellular Traps and Its Implications in Inflammation: An Overview. Front Immunol2017881DOI: 10.3389/fimmu.2017.00081 PMid:28220120 PMCid:PMC5292617
VíctorVMEspulguesJ VHernández-MijaresARochaMOxidative stress and mitochondrial dysfunction in sepsis: a potential therapy with mitochondria-targeted antioxidants. Infect Disord Drug Targets2009937689DOI: 10.2174/187152609788922519 PMid:19689380
CromptonMThe mitochondrial permeability transition pore and its role in cell death. Biochem J 341 ( Pt 2),199923349DOI: 10.1042/bj3410233 PMid:10393078 PMCid:PMC1220352
SingerMThe role of mitochondrial dysfunction in sepsis-induced multi-organ failure. Virulence201456672DOI: 10.4161/viru.26907 PMid:24185508 PMCid:PMC3916385
KornilukAKoperOKemonaHDymicka-PiekarskaVFrom inflammation to cancer. Ir J Med Sci20171865762DOI: 10.1007/s11845-016-1464-0 PMid:27156054 PMCid:PMC5323483
NogueiraVHayN Molecular Pathways: Reactive Oxygen Species Homeostasis in Cancer Cells and Implications for Cancer Therapy. Clin Cancer Res20131943094314DOI: 10.1158/1078-0432. CCR-12-1424 PMid:23719265 PMCid:PMC3933310
VučetićMCormeraisYParksSKPouysségurJThe Central Role of Amino Acids in Cancer Redox Homeostasis: Vulnerability Points of the Cancer Redox Code. Front Oncol20177DOI: 10.3389/fonc.2017.00319 PMid:29312889 PMCid:PMC5742588
GaladariSRahmanAPallichankandySThayyullathilFReactive oxygen species and cancer paradox: To promote or to suppress? Free Radic Biol Med2017104144164DOI: 10.1016/j.freeradbiomed.2017.01.004 PMid:28088622
UpadhyayaBLiuYDeyMPhenethyl Isothiocyanate Exposure Promotes Oxidative Stress and Suppresses Sp1 Transcription Factor in Cancer Stem Cells. Int J Mol Sci201920DOI: 10.3390/ijms20051027 PMid:30818757 PMCid:PMC6429440
ChenWZouPZhaoZChenXFanXVinothkumarRCuiRWuFZhangQLiangGJiJSynergistic antitumor activity of rapamycin and EF24 via increasing ROS for the treatment of gastric cancer. Redox Biol2016107889DOI: 10.1016/j.redox.2016.09.006 PMid:27697670 PMCid:PMC5048112
ChenXDaiXZouPChenWRajamanickamVFengCZhugeWQiuCYeQZhangXLiangGCurcuminoid EF24 enhances the anti-tumour activity of Akt inhibitor MK-2206 through ROS-mediated endoplasmic reticulum stress and mitochondrial dysfunction in gastric cancer. Br J Pharmacol201717411311146DOI: 10.1111/bph.13765 PMid:28255993 PMCid:PMC5406301
BakalovaRZhelevZShibataSNikolovaBAokiIHigashiTImpressive Suppression of Colon Cancer Growth by Triple Combination SN38/EF24/Melatonin: "Oncogenic" Versus "Onco-Suppressive" Reactive Oxygen Species. Anticancer Res20173754495458DOI: 10.21873/anticanres.11973
KasukabeTHonmaYOkabe-KadoJHiguchiYKatoNKumakuraSCombined treatment with cotylenin A and phenethyl isothiocyanate induces strong antitumor activity mainly through the induction of ferroptotic cell death in human pancreatic cancer cells. Oncol Rep201636968976DOI: 10.3892/or.2016.4867 PMid:27375275
Ni W-Y Lu H-F Hsu S-C Hsiao Y-P Liu K-C Liu J-Y Ji B-C Hsueh S-C Hung F-M Shang H-S Chung J-G Phenethyl isothiocyanate inhibits in vivo growth of subcutaneous xenograft tumors of human malignant melanoma A375. S2 cells In vivo 2014 28 891 4
ReczekCRChandelNSThe Two Faces of Reactive Oxygen Species in Cancer. Annu Rev Cancer Biol201717998DOI: 10.1146/annurev-cancerbio-041916-065808
AssiMThe differential role of reactive oxygen species in early and late stages of cancer. Am J Physiol Integr Comp Physiol2017313R646R653DOI: 10.1152/ajpregu.00247.2017 PMid:28835450
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