Abstract：
:PARP inhibitors have been widely tested in clinical trials, especially for the treatment of breast cancer and ovarian cancer, and were shown to be highly successful. Because PARP primarily functions in sensing and repairing DNA strand breaks, the therapeutic effect of PARP inhibition is generally believed to be attributed to impaired DNA repair. We here report that oxidative stress is also increased by PARP inhibition and mediates the antitumor effect. We showed that PARP1 is highly expressed in specimens of high grade serous ovarian carcinoma and its activity is required for unperturbed proliferation of ovarian cancer cells. Inhibition or depletion of PARP leads to not only an increase in DNA damage, but also an elevation in the levels of reactive oxygen species (ROS). Importantly, antioxidant N-acetylcysteine (NAC) significantly attenuated the induction of DNA damage and the perturbation of proliferation by PARP inhibition or depletion. We further showed that NADPH oxidases 1 and 4 were significantly upregulated by PARP inhibition and were partially responsible for the induction of oxidative stress. Depletion of NOX1 and NOX4 partially rescued the growth inhibition of PARP1-deficient tumor xenografts. Our findings suggest that in addition to compromising the repair of DNA damage, PARP inhibition or depletion may exert extra antitumor effect by elevating oxidative stress in ovarian cancer cells.
journal_name
Redox Bioljournal_title
Redox biologyauthors
Hou D,Liu Z,Xu X,Liu Q,Zhang X,Kong B,Wei JJ,Gong Y,Shao Cdoi
10.1016/j.redox.2018.03.016subject
Has Abstractpub_date
2018-07-01 00:00:00pages
99-111issn
2213-2317pii
S2213-2317(18)30189-7journal_volume
17pub_type
杂志文章相关文献
Redox Biology文献大全abstract：:Mitogen-activated protein kinase (MAPK) cascades are evolutionarily conserved modules among eukaryotic species that range from yeast, plants, flies to mammals. In eukaryotic cells, reactive oxygen species (ROS) has both physiological and toxic effects. Both MAPK cascades and ROS signaling are involved in plant respons...
journal_title：Redox biology
pub_type： 杂志文章,评审
doi：10.1016/j.redox.2016.12.009
更新日期：2017-04-01 00:00:00
abstract：:Hypertonia is pathognomonic of cerebral palsy (CP), often caused by brain injury before birth. To understand the early driving events of hypertonia, we utilized magnetic resonance imaging (MRI) assessment of early critical brain injury in rabbit fetuses (79% term) that will predict hypertonia after birth following ant...
journal_title：Redox biology
pub_type： 杂志文章
doi：10.1016/j.redox.2019.101407
更新日期：2020-01-01 00:00:00
abstract：:Cells employ multiple defence mechanisms to sustain a wide range of stress conditions associated with accumulation of modified self-biomolecules leading to lipo- and proteotoxicity. One of such mechanisms involves activation of the autophagy-lysosomal pathway for removal and degradation of modified lipids, proteins an...
journal_title：Redox biology
pub_type： 杂志文章
doi：10.1016/j.redox.2019.101123
更新日期：2019-05-01 00:00:00
abstract：:Autophagy is an important cell recycling program responsible for the clearance of damaged or long-lived proteins and organelles. Pharmacological modulators of this pathway have been extensively utilized in a wide range of basic research and pre-clinical studies. Bafilomycin A1 and chloroquine are commonly used compoun...
journal_title：Redox biology
pub_type： 杂志文章
doi：10.1016/j.redox.2016.11.004
更新日期：2017-04-01 00:00:00
abstract：:Cigarette smoking remains a major health concern worldwide, and many of the adverse effects of cigarette smoke (CS) can be attributed to its abundant electrophilic aldehydes, such as acrolein (2-propenal). Previous studies indicate that acrolein readily reacts with thioredoxin reductase 1 (TrxR1), a critical enzyme in...
journal_title：Redox biology
pub_type： 杂志文章
doi：10.1016/j.redox.2013.02.001
更新日期：2013-02-22 00:00:00
abstract：:Cells evolved robust homeostatic mechanisms to protect against oxidation or alkylation by electrophilic species. Glutathione (GSH) is the most abundant intracellular thiol, protects cellular components from oxidation and is maintained in a reduced state by glutathione reductase (GR). Nitro oleic acid (NO2-OA) is an el...
journal_title：Redox biology
pub_type： 杂志文章
doi：10.1016/j.redox.2018.11.008
更新日期：2019-02-01 00:00:00
abstract：:Myo-satellite cells regenerate and differentiate into skeletal muscle (SM) after acute or chronic injury. Changes in the redox milieu towards the oxidative arm at the wound site are known to compromise SM regeneration. Recently, we reported that abrogation of Nrf2/antioxidant signaling promotes oxidative stress and im...
journal_title：Redox biology
pub_type： 杂志文章
doi：10.1016/j.redox.2020.101492
更新日期：2020-07-01 00:00:00
abstract：:We present a new database, specifically devoted to ROS homeostasis regulated proteins. This database replaced our previous database, the PeroxiBase, which was focused only on various peroxidase families. The addition of 20 new protein families related with ROS homeostasis justifies the new name for this more complex a...
journal_title：Redox biology
pub_type： 杂志文章
doi：10.1016/j.redox.2019.101247
更新日期：2019-09-01 00:00:00
abstract：:Red blood cells (RBC) have been considered almost exclusively as a transporter of metabolic gases and nutrients for the tissues. It is an accepted dogma that RBCs take up and inactivate endothelium-derived NO via rapid reaction with oxyhemoglobin to form methemoglobin and nitrate, thereby limiting NO available for vas...
journal_title：Redox biology
pub_type： 杂志文章,评审
doi：10.1016/j.redox.2013.12.027
更新日期：2014-01-09 00:00:00
abstract：:Williamson and colleagues present important data on the effects of MitoQ - an antioxidant compound targeted to mitochondria - on mtDNA damage following exercise. Future studies are needed to elucidate, whether or not the observed prevention of MitoQ on DNA damage is beneficial with regard to functional outcomes in hea...
journal_title：Redox biology
pub_type： 杂志文章
doi：10.1016/j.redox.2020.101732
更新日期：2021-01-01 00:00:00
abstract：:Redox signaling and oxidative stress are associated with tissue fibrosis and aging. Aging is recognized as a major risk factor for fibrotic diseases involving multiple organ systems, including that of the lung. A number of oxidant generating enzymes are upregulated while antioxidant defenses are deficient with aging a...
journal_title：Redox biology
pub_type： 杂志文章,评审
doi：10.1016/j.redox.2016.06.005
更新日期：2016-10-01 00:00:00
abstract：:The precise molecular events defining the complex role of oxidative stress in the inactivation of the cerebral sodium pump in radical-induced neurodegenerative diseases is yet to be fully clarified and thus still open. Herein we investigated the modulation of the activity of the cerebral transmembrane electrogenic enz...
journal_title：Redox biology
pub_type： 杂志文章
doi：10.1016/j.redox.2014.12.015
更新日期：2015-01-01 00:00:00
abstract：:Mitochondria are cellular energy powerhouses that play important roles in maintaining cell survival, cell death and cellular metabolic homeostasis. Timely removal of damaged mitochondria via autophagy (mitophagy) is thus critical for cellular homeostasis and function. Mitochondria are reticular organelles that have hi...
journal_title：Redox biology
pub_type： 杂志文章,评审
doi：10.1016/j.redox.2014.11.006
更新日期：2015-01-01 00:00:00
abstract：:Gallbladder cancer (GBC) is a highly malignant bile duct cancer with poor prognosis characterized by its insensitivity to chemotherapy. Emerging evidence indicates that cytoprotective antioxidation is involved in drug resistance of various cancers; however, the underlying molecular mechanisms remain obscure. Here, we ...
journal_title：Redox biology
pub_type： 杂志文章
doi：10.1016/j.redox.2019.101149
更新日期：2019-04-01 00:00:00
abstract：:Reactive oxygen and nitrogen species (e.g. H2O2, nitric oxide) confer redox regulation of essential cellular signaling pathways such as cell differentiation, proliferation, migration and apoptosis. In addition, classical regulation of gene expression or activity, including gene transcription to RNA followed by transla...
journal_title：Redox biology
pub_type： 杂志文章,评审
doi：10.1016/j.redox.2015.05.008
更新日期：2015-08-01 00:00:00
abstract：:Highly active anti-retrovirus therapy (HAART) has been used to block the progression and symptoms of human immunodeficiency virus infection. Although it decreases morbidity and mortality, clinical use of HAART has also been linked to various adverse effects such as severe cardiomyopathy resulting from compromised mito...
journal_title：Redox biology
pub_type： 杂志文章
doi：10.1016/j.redox.2017.06.011
更新日期：2017-10-01 00:00:00
abstract：:Oxidative stress plays a major part in the pathogenesis of drug-induced liver injury. Yet, overcoming it with other xenobiotics impose additional risks. In this study, we consider the use of natural-occurring and purified Vitamin E analogs as hepatoprotective agents. Vitamin E is well-known for its intrinsic antioxida...
journal_title：Redox biology
pub_type： 杂志文章
doi：10.1016/j.redox.2015.01.013
更新日期：2015-01-01 00:00:00
abstract：:Exposure to the space radiation environment poses risks for a range of deleterious health effects due to the unique types of radiation encountered. Galactic cosmic rays are comprised of a spectrum of highly energetic nuclei that deposit densely ionizing tracks of damage along the particle trajectory. These tracks are ...
journal_title：Redox biology
pub_type： 杂志文章
doi：10.1016/j.redox.2015.03.001
更新日期：2015-08-01 00:00:00
abstract：:The inducible form of Heme Oxygenase-1 (HO-1), a major endoplasmic reticulum (ER) associated heme protein, is known to play important roles in protection against oxidative and chemical stress by degrading free heme released from degradation of heme proteins. In this study we show that induced expression of HO-1 by sub...
journal_title：Redox biology
pub_type： 杂志文章
doi：10.1016/j.redox.2013.07.004
更新日期：2013-07-23 00:00:00
abstract：BACKGROUND:The oxidation of the methionine adenosyltransferase (MAT) by the combined impact of peroxides contaminating parenteral nutrition (PN) and oxidized redox potential of glutathione is suspected to explain its inhibition observed in animals. A modification of MAT activity is suspected to be at origin of the PN-a...
journal_title：Redox biology
pub_type： 杂志文章
doi：10.1016/j.redox.2015.12.003
更新日期：2016-08-01 00:00:00
abstract：:Oxidation-reduction chemistry is fundamental to the metabolism of all living organisms, and hence quantifying the principal redox players is important for a comprehensive understanding of cell metabolism in normal and pathological states. In mammalian cells, this is accomplished by measuring oxygen partial pressure (p...
journal_title：Redox biology
pub_type： 杂志文章
doi：10.1016/j.redox.2020.101549
更新日期：2020-07-01 00:00:00
abstract：:Keloids exhibit metabolic reprogramming including enhanced glycolysis and attenuated oxidative phosphorylation. Hypoxia induces a series of protective responses in mammalian cells. However, the metabolic phenotype of keloid fibroblasts under hypoxic conditions remains to be elucidated. The present study aimed to inves...
journal_title：Redox biology
pub_type： 杂志文章
doi：10.1016/j.redox.2020.101815
更新日期：2021-01-01 00:00:00
abstract：:Dietary nitrate is now recognized as an alternative substrate for nitric oxide (•NO) production in the gut. This novel pathway implies the sequential reduction of nitrate to nitrite, •NO and other bioactive nitrogen oxides but the physiological relevance of these oxidants has remained elusive. We have previously shown...
journal_title：Redox biology
pub_type： 杂志文章
doi：10.1016/j.redox.2016.04.002
更新日期：2016-08-01 00:00:00
abstract：:Hypoxia, a common element in the tumor environment, leads to Hypoxia-Inducible Factor-1α (HIF-1α) stabilization to modulate cellular metabolism as an adaptive response. In a previous study, we showed that inhibition of the nuclear factor erythroid 2-like-2 (NFE2L2; NRF2), a master regulator of many genes coping with e...
journal_title：Redox biology
pub_type： 杂志文章
doi：10.1016/j.redox.2019.101210
更新日期：2019-06-01 00:00:00
abstract：:Oxidative stress resulting from the accumulation of high levels of reactive oxygen species is a salient feature of, and a well-recognised pathological factor for, diverse pathologies. One common mechanism for oxidative stress damage is via the disruption of intracellular ion homeostasis to induce cell death. TRPM2 is ...
journal_title：Redox biology
pub_type： 杂志文章,评审
doi：10.1016/j.redox.2020.101755
更新日期：2020-10-01 00:00:00
abstract：:Oxidative stress is reported to regulate several apoptotic and necrotic cell death pathways in auditory tissues. Poly(ADP-ribose) polymerase-1 (PARP-1) can be activated under oxidative stress, which is the hallmark of parthanatos. Autophagy, which serves either a pro-survival or pro-death function, can also be stimula...
journal_title：Redox biology
pub_type： 杂志文章
doi：10.1016/j.redox.2017.10.002
更新日期：2018-04-01 00:00:00
abstract：:The notion that oxidative stress plays a role in virtually every human disease and environmental exposure has become ingrained in everyday knowledge. However, mounting evidence regarding the lack of specificity of biomarkers traditionally used as indicators of oxidative stress in human disease and exposures now necess...
journal_title：Redox biology
pub_type： 杂志文章,meta分析
doi：10.1016/j.redox.2017.03.024
更新日期：2017-08-01 00:00:00
abstract：:Mechanistic/mammalian target of rapamycin (mTOR) has emerged as a new potential therapeutic target for gastric cancer. Rapamycin and rapamycin analogs are undergoing clinical trials and have produced clinical responses in a subgroup of cancer patients. However, monotherapy with rapamycin at safe dosage fails to induce...
journal_title：Redox biology
pub_type： 杂志文章
doi：10.1016/j.redox.2016.09.006
更新日期：2016-12-01 00:00:00
abstract：:Nitrite and nitrate restore deficient endogenous nitric oxide (NO) production as they are converted back to NO, and therefore complement the classic enzymatic NO synthesis. Circulating nitrate and nitrite must cross membrane barriers to produce their effects and increased nitrate concentrations may attenuate the nitri...
journal_title：Redox biology
pub_type： 杂志文章
doi：10.1016/j.redox.2017.03.003
更新日期：2017-08-01 00:00:00
abstract：:Vascular peroxidase 1 (VPO1) is a member of the peroxidase family which aggravates oxidative stress by producing hypochlorous acid (HOCl). Our previous study demonstrated that VPO1 plays a critical role in endothelial dysfunction through dimethylarginine dimethylaminohydrolase2 (DDAH2)/asymmetric Dimethylarginine (ADM...
journal_title：Redox biology
pub_type： 杂志文章
doi：10.1016/j.redox.2017.02.022
更新日期：2017-08-01 00:00:00
