scholarly journals Blockade of Histone Deacetylase Inhibitor-Induced RelA/p65 Acetylation and NF-κB Activation Potentiates Apoptosis in Leukemia Cells through a Process Mediated by Oxidative Damage, XIAP Downregulation, and c-Jun N-Terminal Kinase 1 Activation

2005 ◽  
Vol 25 (13) ◽  
pp. 5429-5444 ◽  
Author(s):  
Yun Dai ◽  
Mohamed Rahmani ◽  
Paul Dent ◽  
Steven Grant
Keyword(s):  
Oxidative Damage ◽  
Nuclear Translocation ◽  
Hdac Inhibitors ◽  
Histone Acetyltransferases ◽  
Leukemia Cells ◽  
Ros Generation ◽  
Suberoylanilide Hydroxamic Acid ◽  
Oxygen Species ◽  
Antiapoptotic Proteins ◽  
Deacetylase Inhibitor

ABSTRACT NF-κB activation is reciprocally regulated by RelA/p65 acetylation and deacetylation, which are mediated by histone acetyltransferases (HATs) and deacetylases (HDACs). Here we demonstrate that in leukemia cells, NF-κB activation by the HDAC inhibitors (HDACIs) MS-275 and suberoylanilide hydroxamic acid was associated with hyperacetylation and nuclear translocation of RelA/p65. The latter events, as well as the association of RelA/p65 with IκBα, were strikingly diminished by either coadministration of the IκBα phosphorylation inhibitor Bay 11-7082 (Bay) or transfection with an IκBα superrepressor. Inhibition of NF-κB by pharmacological inhibitors or genetic strategies markedly potentiated apoptosis induced by HDACIs, and this was accompanied by enhanced reactive oxygen species (ROS) generation, downregulation of Mn-superoxide dismutase and XIAP, and c-Jun N-terminal kinase 1 (JNK1) activation. Conversely, N-acetyl l-cysteine blocked apoptosis induced by Bay/HDACIs by abrogating ROS generation. Inhibition of JNK1 activation attenuated Bay/HDACI lethality without affecting NF-κB inactivation and ROS generation. Finally, XIAP overexpression dramatically protected cells against the Bay/HDACI regimen but failed to prevent ROS production and JNK1 activation. Together, these data suggest that HDACIs promote the accumulation of acetylated RelA/p65 in the nucleus, leading to NF-κB activation. Moreover, interference with these events by either pharmacological or genetic means leads to a dramatic increase in HDACI-mediated lethality through enhanced oxidative damage, downregulation of NF-κB-dependent antiapoptotic proteins, and stress-related JNK1 activation.

scholarly journals Acetylshikonin Induces Apoptosis in Human Colorectal Cancer HCT-15 and LoVo Cells via Nuclear Translocation of FOXO3 and ROS Level Elevation

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Heui Min Lim ◽  
Jongsung Lee ◽  
Myeong Jin Nam ◽  
See-Hyoung Park
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Nuclear Translocation ◽  
Ros Generation ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Human Colorectal Cancer ◽  
Antiproliferative Effects ◽  
Lovo Cells ◽  
Colorectal Cancer Cells

Acetylshikonin, a naphthoquinone, is a pigment compound derived from Arnebia sp., which is known for its anti-inflammatory potential. However, its anticarcinogenic effect has not been well investigated. Thus, in this study, we focused on investigating its apoptotic effects against HCT-15 and LoVo cells, which are human colorectal cancer cells. MTT assay, cell counting assay, and colony formation assay have shown acetylshikonin treatment induced cytotoxic and antiproliferative effects against colorectal cancer cells in a dose- and time-dependent manner. DNA fragmentation was observed via terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Also, the increase of subG1 phase in cell cycle arrest assay and early/late apoptotic rates in annexin V/propidium iodide (PI) double staining assay was observed, which indicates an apoptotic potential of acetylshikonin against colorectal cancer cells. 2 ′ ,7 ′ -Dichlorofluorescin diacetate (DCF-DA) staining was used to evaluate reactive oxygen species (ROS) generation in acetylshikonin-treated colorectal cancer cells. Fluorescence-activated cell sorting (FACS) analysis showed that acetylshikonin induced an increase in reactive oxygen species (ROS) levels and apoptotic rate in a dose- and time-dependent manner in HCT-15 and LoVo cells. In contrast, cotreatment with N-acetyl cysteine (NAC) has reduced ROS generation and antiproliferative effects in colorectal cancer cells. Western blotting analysis showed that acetylshikonin treatment induced increase of cleaved PARP, γH2AX, FOXO3, Bax, Bim, Bad, p21, p27, and active forms of caspase-3, caspase-7, caspase-9, caspase-6, and caspase-8 protein levels, while those of inactive forms were decreased. Also, the expressions of pAkt, Bcl-2, Bcl-xL, peroxiredoxin, and thioredoxin 1 were decreased. Furthermore, western blotting analysis of cytoplasmic and nuclear fractionated proteins showed that acetylshikonin treatment induced the nuclear translocation of FOXO3, which might result from DNA damage by the increased intracellular ROS level. This study represents apoptotic potential of acetylshikonin against colorectal cancer cells via translocation of FOXO3 to the nucleus and upregulation of ROS generation.

The Requirement of Reactive Oxygen Species Generation in the Apoptosis of Leukemia Cells Induced by 2-Methoxyestradiol.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4370-4370
Author(s):  
Guo Kunyuan ◽  
Miaorong She ◽  
Haiyan Hu ◽  
Xinqing Niu ◽  
Sanfang Tu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Leukemia Cell ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Leukemic Cells ◽  
Leukemia Cells ◽  
Ros Generation ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Induced Apoptosis

Abstract 2-Methoxyestradiol (2-ME) is a new anticancer agent currently under investigation for treatment of leukemia. We evaluated the effects of 2-ME-induced apoptosis in two myeloid leukemia cell lines (U937 and HL-60) in association with reactive oxygen species (ROS) generation. We found that 2-ME resulted in viability decrease in a dose-dependent manner, generated ROS: nitric oxide and superoxide anions, and mitochondria damage. 2-ME-induced apoptosis correlated with increase in ROS. Quenching of ROS with N-acetyl-L-cysteine protected leukemia cells from the cytotoxicity of 2-ME and prevented apoptosis induction by 2-ME. Furthermore, addition of manumycin, a farnesyltransferase inhibitor, demonstrated by our previous studies that induced apoptosis of leukemic cells and induced ROS, significantly enhanced the apoptosis-induced by 2-ME. In conclusion, cellular ROS generation play an important role in the cytotoxic effect of 2-ME. It is possible to use ROS-generation agents such as manumycin to enhance the antileukemic effect. Such a combination strategy need the further in vivo justify and may have potential clinical application.

scholarly journals Lico A Enhances Nrf2-Mediated Defense Mechanisms againstt-BHP-Induced Oxidative Stress and Cell Death via Akt and ERK Activation in RAW 264.7 Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Hongming Lv ◽  
Hua Ren ◽  
Lidong Wang ◽  
Wei Chen ◽  
Xinxin Ci
Keyword(s):  
Oxidative Damage ◽  
Nuclear Translocation ◽  
Antioxidant Activities ◽  
Biological Properties ◽  
Raw 264.7 Cells ◽  
Ros Generation ◽  
Heme Oxygenase 1 ◽  
Raw 264.7 ◽  
Related Factor ◽  
Glutamate Cysteine Ligase

Licochalcone A (Lico A) exhibits various biological properties, including anti-inflammatory and antioxidant activities. In this study, we investigated the antioxidative potential and mechanisms of Lico A againsttert-butyl hydroperoxide- (t-BHP-) induced oxidative damage in RAW 264.7 cells. Our results indicated that Lico A significantly inhibitedt-BHP-induced cytotoxicity, apoptosis, and reactive oxygen species (ROS) generation and reduced glutathione (GSH) depletion but increased the glutamate-cysteine ligase modifier (GCLM) subunit and the glutamate-cysteine ligase catalytic (GCLC) subunit genes expression. Additionally, Lico A dramatically upregulated the antioxidant enzyme heme oxygenase 1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2), which were associated with inducing Nrf2 nuclear translocation, decreasing Keap1 protein expression and increasing antioxidant response element (ARE) promoter activity. Lico A also obviously induced the activation of serine/threonine kinase (Akt) and extracellular signal-regulated kinase (ERK), but PI3K/Akt and ERK inhibitors treatment displayed clearly decreased levels of LicoA-induced Nrf2 nuclear translocation and HO-1 expression, respectively. Furthermore, Lico A treatment markedly attenuatedt-BHP-induced oxidative damage, which was reduced by treatment with PI3K/Akt, ERK, and HO-1 inhibitors. Therefore, Lico A might have a protective role againstt-BHP-induced cytotoxicity by modulating HO-1 and by scavenging ROS via the activation of the PI3K/Akt and ERK/Nrf2 signaling pathways.

scholarly journals ANTIOXIDATIVE DEFENSE RESPONSE TO APHID-INDUCED OXIDATIVE STRESS IN Glycine max (L.) Merr. cv. “Nam Dan”

2016 ◽  
Vol 54 (6) ◽  
pp. 719 ◽  
Author(s):  
Tran Ngoc Toan ◽  
Tran Thi Van Thanh Huyen ◽  
Mai Van Chung
Keyword(s):  
Oxidative Stress ◽  
Glycine Max ◽  
Oxidative Damage ◽  
Thiobarbituric Acid ◽  
Ros Generation ◽  
Oxygen Species ◽  
Thiobarbituric Acid Reactive Substances ◽  
Aphis Craccivora Koch ◽  
Glycine Max L ◽  
Aphid Feeding

Infestation of cowpea aphid (Aphis craccivora Koch) induced oxidative stress in leaves of soybean (Glycine max (L.) Merr. cv. “Nam Dan”) with a burst in generation of reactive oxygen species (ROS) products such as superoxide anion radical (O2.-) and hydrogen peroxide (H2O2) recorded around 24 hours after aphid feeding. An increase in content of thiobarbituric acid reactive substances (TBARS) in lipid peroxidation and a defined percentage of injury in aphid-infested leaves were resulted from the cellular oxidative damage. The enhanced activity of the antioxidant enzymes such as superoxide dismutase (SOD, EC 1.15.1.1) and catalase (CAT, EC 1.11.1.6) in leaves of soybean “Nam Dan” functions as the antioxidative response that controlled both ROS-generation to be enough levels to play as defensive element and ROS-detoxifying to reduce aphid-induced oxidative damage. The enhancement of SOD and CAT also can improve the tolerance of soybean “Nam Dan” to impact from A. craccivora.

scholarly journals Regulation of Reactive Oxygen Species and Antioxidant Defense in Plants under Salinity

2021 ◽  
Vol 22 (17) ◽  
pp. 9326
Author(s):  
Mirza Hasanuzzaman ◽  
Md. Rakib Hossain Raihan ◽  
Abdul Awal Chowdhury Masud ◽  
Khussboo Rahman ◽  
Farzana Nowroz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Salt Stress ◽  
Oxidative Damage ◽  
Antioxidant Defense ◽  
Reactive Oxygen ◽  
Antioxidant Defense System ◽  
Ros Generation ◽  
Oxygen Species ◽  
Defense System

The generation of oxygen radicals and their derivatives, known as reactive oxygen species, (ROS) is a part of the signaling process in higher plants at lower concentrations, but at higher concentrations, those ROS cause oxidative stress. Salinity-induced osmotic stress and ionic stress trigger the overproduction of ROS and, ultimately, result in oxidative damage to cell organelles and membrane components, and at severe levels, they cause cell and plant death. The antioxidant defense system protects the plant from salt-induced oxidative damage by detoxifying the ROS and also by maintaining the balance of ROS generation under salt stress. Different plant hormones and genes are also associated with the signaling and antioxidant defense system to protect plants when they are exposed to salt stress. Salt-induced ROS overgeneration is one of the major reasons for hampering the morpho-physiological and biochemical activities of plants which can be largely restored through enhancing the antioxidant defense system that detoxifies ROS. In this review, we discuss the salt-induced generation of ROS, oxidative stress and antioxidant defense of plants under salinity.

scholarly journals Apoptotic Effects of Anthocyanins from Vitis coignetiae Pulliat Are Enhanced by Augmented Enhancer of the Rudimentary Homolog (ERH) in Human Gastric Carcinoma MKN28 Cells

2021 ◽  
Vol 22 (6) ◽  
pp. 3030
Author(s):  
Cheol Park ◽  
Won Sup Lee ◽  
Se-Il Go ◽  
Sang-Ho Jeong ◽  
Jiyun Yoo ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Ros Generation ◽  
Human Gastric Cancer ◽  
Oxygen Species ◽  
Mitochondrial Depolarization ◽  
Gastric Cancer Cells ◽  
Anticancer Efficacy ◽  
Antiapoptotic Proteins ◽  
Apoptotic Effect ◽  
Apoptotic Effects

Evidence suggests that augmented expression of a certain gene can influence the efficacy of targeted and conventional chemotherapies. Here, we tested whether the high expression of enhancer of the rudimentary homolog (ERH), which serves as a prognostic factor in some cancers, can influence the efficacy of anthocyanins isolated from fruits of Vitis coignetiae Pulliat, Meoru in Korea (AIMs) on human gastric cancer cells. The anticancer efficacy of AIMs was augmented in ERH-transfected MKN28 cells (E-MKN28 cells). Molecularly, ERH augmented AIM-induced caspase-dependent apoptosis by activating caspase-3 and -9. The ERH-augmented apoptotic effect was related to mitochondrial depolarization and inhibition of antiapoptotic proteins, XIAP, and Bcl-2. In addition, reactive oxygen species (ROS) generation was augmented in AIMs-treated E-MKN28 cells compared to AIMs-treated naïve MKN28 cells. In conclusion, ERH augmented AIM-induced caspase-dependent mitochondrial-related apoptosis in MKN28 cells. A decrease in expression of Bcl-2 and subsequent excessive ROS generation would be the mechanism for ERH-augmented mitochondrial-related apoptosis in AIMs-treated MKN28 cells. A decrease in expression of XIAP would be another mechanism for ERH-augmented caspase-dependent apoptosis in AIMs-treated MKN28 cells.

scholarly journals Fucoxanthin Exerts Cytoprotective Effects against Hydrogen Peroxide-induced Oxidative Damage in L02 Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Xia Wang ◽  
Yan-jun Cui ◽  
Jia Qi ◽  
Min-min Zhu ◽  
Tian-liang Zhang ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Oxidative Damage ◽  
Liver Diseases ◽  
Nuclear Translocation ◽  
Reduced Glutathione ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Protein Levels ◽  
Intracellular Ros ◽  
L02 Cells

Several previous studies have demonstrated the excellent antioxidant activity of fucoxanthin against oxidative stress which is closely related to the pathogenesis of liver diseases. The present work was to investigate whether fucoxanthin could protect human hepatic L02 cells against hydrogen peroxide- (H2O2-) induced oxidative damage. Its effects on H2O2-induced cell viability, lactate dehydrogenase (LDH) leakage, intracellular reduced glutathione, and reactive oxygen species (ROS) contents, along with mRNA and protein relative levels of the cytoprotective genes including Nrf2, HO-1, and NQO1, were investigated. The results showed that fucoxanthin could upregulate the mRNA and protein levels of the cytoprotective genes and promote the nuclear translocation of Nrf2, which could be inhibited by the PI3K inhibitor of LY294002. Pretreatment of fucoxanthin resulted in decreased LDH leakage and intracellular ROS content but enhanced intracellular reduced glutathione. Interestingly, pretreatment using fucoxanthin protected against the oxidative damage in a nonconcentration-dependent manner, with fucoxanthin of 5 μM demonstrating the optimal effects. The results suggest that fucoxanthin exerts cytoprotective effects against H2O2-induced oxidative damage in L02 cells, which may be through the PI3K-dependent activation of Nrf2 signaling.

scholarly journals Spinal Reactive Oxygen Species and Oxidative Damage Mediate Chronic Pain in Lame Dairy Cows

Animals ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 693 ◽  
Author(s):  
Daniel Herzberg ◽  
Pablo Strobel ◽  
Ricardo Chihuailaf ◽  
Alfredo Ramirez-Reveco ◽  
Heine Müller ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Spinal Cord ◽  
Chronic Pain ◽  
Oxidative Damage ◽  
Dairy Cows ◽  
Antioxidant System ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Oxygen Species ◽  
Carbonyl Groups

Lameness in dairy cows is a worldwide prevalent disease with a negative impact on animal welfare and herd economy. Oxidative damage and antioxidant system dysfunction are common features of many CNS diseases, including chronic pain. The aim of this study was to evaluate the levels of reactive oxygen species (ROS) and oxidative damage markers in the spinal cord of dairy cows with chronic inflammatory lameness. Locomotion score was performed in order to select cows with chronic lameness. Dorsal horn spinal cord samples were obtained post mortem from lumbar segments (L2–L5), and ROS, malondialdehyde (MDA), and carbonyl groups were measured along with the activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and total antioxidant response (TAR). Lame cows had increased levels of ROS, MDA, and carbonyl groups, while no differences were observed between lame and non-lame cows in SOD, GPx, CAT, and TAR activity. We conclude that painful chronic inflammatory lameness in dairy cows is associated with an increase in ROS, MDA, and carbonyl groups. Nonetheless, an association between ROS generation and dysfunction of the antioxidant system, as previously proposed, could not be established.

An integrated view of oxidative stress in aging: basic mechanisms, functional effects, and pathological considerations

2007 ◽  
Vol 292 (1) ◽  
pp. R18-R36 ◽  
Author(s):  
Kevin C. Kregel ◽  
Hannah J. Zhang
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Physiological Function ◽  
Ros Generation ◽  
Oxygen Species ◽  
Stress Theory ◽  
Complex Process ◽  
Potential Impact ◽  
Critical Aspects

Aging is an inherently complex process that is manifested within an organism at genetic, molecular, cellular, organ, and system levels. Although the fundamental mechanisms are still poorly understood, a growing body of evidence points toward reactive oxygen species (ROS) as one of the primary determinants of aging. The “oxidative stress theory” holds that a progressive and irreversible accumulation of oxidative damage caused by ROS impacts on critical aspects of the aging process and contributes to impaired physiological function, increased incidence of disease, and a reduction in life span. While compelling correlative data have been generated to support the oxidative stress theory, a direct cause-and-effect relationship between the accumulation of oxidatively mediated damage and aging has not been strongly established. The goal of this minireview is to broadly describe mechanisms of in vivo ROS generation, examine the potential impact of ROS and oxidative damage on cellular function, and evaluate how these responses change with aging in physiologically relevant situations. In addition, the mounting genetic evidence that links oxidative stress to aging is discussed, as well as the potential challenges and benefits associated with the development of antiaging interventions and therapies.

Benzene metabolites enhance reactive oxygen species generation in HL60 human leukemia cells

1996 ◽  
Vol 15 (5) ◽  
pp. 422-427 ◽  
Author(s):  
Y. Shen ◽  
H-M. Shen ◽  
C-Y. Shi ◽  
C-N. Ong
Keyword(s):  
Reactive Oxygen Species ◽  
Lipid Peroxidation ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Leukemia Cells ◽  
Ros Generation ◽  
Human Leukemia ◽  
Ros Production ◽  
Oxygen Species ◽  
Ros Formation

Benzene is myelotoxic and leukemogenic in humans. The mechanisms leading to these effects, however have not been fully elucidated. One of the underlying mechanisms is believed to be the oxidative damage caused by its metabolites. A comparative study was undertaken to examine the relationships between reactive oxygen species (ROS) production, lipid peroxidation and subse quent cytotoxicity induced by five major benzene meta bolites. The generation of ROS by benzene metabolites was demonstrated by the significant and dose-dependent increase of intracellular ROS formation in HL60 human promyelocytic leukemia cells in vitro. 1,4-Benzoquinone (BQ) was found to be the most potent metabolite in induction of ROS formation, followed by 1,2,4-benzene triol (BT) and to a lesser extent, phenol (PH) and trans, trans-muconaldehyde (MD). No significant effect was observed when the cells were treated with trans, trans-muconic acid (MA). The enhancement of ROS production by BQ was effectively inhibited by the addition of catalase, deferoxamine (DFO) and dimethyl sulfoxide (DMSO), but unchanged by superoxide dismutase (SOD), suggest that hydrogen peroxide (H2O2) and hydroxyl radicals (OH.) are the two major forms of ROS involved. The results also demonstrate that the ability of benzene metabolites in enhancing ROS generation is closely correlated to their capacity in causing lipid peroxidation and subsequent cytotoxicity. These findings together with earlier parallel observations on DNA damage suggest that ROS play an important role in the mechanism of carcinogenesis induced by benzene metabolites.

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