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Article: High Glucose Level Impairs Human Mature Bone Marrow Adipocyte Function Through Increased ROS Production.

Rharass, Tareck / Lucas, Stéphanie

2019 Volume 10, Page(s) 607

Abstract: Bone marrow adipocytes (BMAds) accumulate in aging, menopause, and metabolic diseases such as Type 2 diabetes. These osteoporotic conditions are associated with oxidative stress and hyperglycemia which are both considered as critical factors underlying ... ...

Abstract	Bone marrow adipocytes (BMAds) accumulate in aging, menopause, and metabolic diseases such as Type 2 diabetes. These osteoporotic conditions are associated with oxidative stress and hyperglycemia which are both considered as critical factors underlying bone fragility. Glucose excess and reactive oxygen species (ROS) are known to favor adipogenesis over osteoblastogenesis. In this study, we investigated whether high glucose exposure could determine dysfunction of mature BMAds, specifically through ROS production. The effects of low (LG, 5 mM) or high glucose (HG, 25 mM) concentrations were examined using human bone mesenchymal stromal cells (hBMSCs) in the time course of differentiation, and, up to 21 days once adipocytes were mature. HG did not alter the adipocyte differentiation process of hBMSCs. Yet, after 21 days under HG exposure,
Language	English
Publishing date	2019-09-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2019.00607
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Article ; Online: MECHANISMS IN ENDOCRINOLOGY: Bone marrow adiposity and bone, a bad romance?

Rharass, Tareck / Lucas, Stéphanie

European journal of endocrinology

2018 Volume 179, Issue 4, Page(s) R165–R182

Abstract: Bone marrow adipocytes (BMA-) constitute an original and heterogeneous fat depot whose development appears interlinked with bone status throughout life. The gradual replacement of the haematopoietic tissue by BMA arises in a well-ordered way during ... ...

Abstract	Bone marrow adipocytes (BMA-) constitute an original and heterogeneous fat depot whose development appears interlinked with bone status throughout life. The gradual replacement of the haematopoietic tissue by BMA arises in a well-ordered way during childhood and adolescence concomitantly to bone growth and continues at a slower rate throughout the adult life. Importantly, BM adiposity quantity is found well associated with bone mineral density (BMD) loss at different skeletal sites in primary osteoporosis such as in ageing or menopause but also in secondary osteoporosis consecutive to anorexia nervosa. Since BMA and osteoblasts originate from a common mesenchymal stem cell, adipogenesis is considered as a competitive process that disrupts osteoblastogenesis. Besides, most factors secreted by bone and bone marrow cells (ligands and antagonists of the WNT/β-catenin pathway, BMP and others) reciprocally regulate the two processes. Hormones such as oestrogens, glucocorticoids, parathyroid and growth hormones that control bone remodelling also modulate the differentiation and the activity of BMA. Actually, BMA could also contribute to bone loss through the release of paracrine factors altering osteoblast and/or osteoclast formation and function. Based on clinical and fundamental studies, this review aims at presenting and discussing these current arguments that support but also challenge the involvement of BMA in the bone mass integrity.
MeSH term(s)	Adipocytes ; Adipogenesis/physiology ; Adipose Tissue ; Adiposity ; Bone Density ; Bone Marrow ; Bone Marrow Cells ; Bone Morphogenetic Proteins/metabolism ; Bone Remodeling/physiology ; Cell Differentiation/physiology ; Estrogens/metabolism ; Glucocorticoids/metabolism ; Human Growth Hormone/metabolism ; Humans ; Mesenchymal Stromal Cells ; Osteoblasts ; Osteogenesis/physiology ; Osteoporosis/physiopathology ; Parathyroid Hormone/metabolism ; Wnt Signaling Pathway
Chemical Substances	Bone Morphogenetic Proteins ; Estrogens ; Glucocorticoids ; Parathyroid Hormone ; Human Growth Hormone (12629-01-5)
Language	English
Publishing date	2018-10-01
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1183856-5
ISSN	1479-683X ; 0804-4643
ISSN (online)	1479-683X
ISSN	0804-4643
DOI	10.1530/EJE-18-0182
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Article ; Online: A comparative study of Caesalpinia bonduc (L.) Roxb. root extracts on sexual behaviour in male Wistar rats.

Sindete, Mariette / Rharass, Tareck / Gbankoto, Adam / Yemoa, Achille / Ganfon, Habib / Adjagba, Marius / Ribou, Anne-Cécile

Andrologia

2021 Volume 53, Issue 7, Page(s) e14072

Abstract: Caesalpinia bonduc is among the traditionally used plant in Benin, for its enhancement of male sexual activity. This study was undertaken to investigate the potential effect of C. bonduc root extracts on sexual behaviour of male Wistar rats. For that, ... ...

Abstract	Caesalpinia bonduc is among the traditionally used plant in Benin, for its enhancement of male sexual activity. This study was undertaken to investigate the potential effect of C. bonduc root extracts on sexual behaviour of male Wistar rats. For that, thirty-six rats were allocated into six groups and orally treated with dimethyl sulfoxide (control), Sildenafil citrate (standard) and C. bonduc root extracts (hexane, ethyl acetate, ethanol and methanol) orally for twenty-eight days. Sexual behaviour parameters such as intromission frequency, intromission latency, mount latency and mount frequency were evaluated on day 0, 14 and 28. After the study completion, the body and reproductive organ weights as well as testicular histology and testosterone level were recorded. C. bonduc root extracts treatments had no significant effect on the body weight of rats. Enhancement in sexual behaviour was observed in ethanolic extract treated rats. An significant increase in mount frequency and intromission frequency as well as significant reduction in mount latency and intromission latency were noticed for ethanolic extract. The same extract caused an improvement in testosterone levels, relative testes weight and histological architecture. The findings demonstrate the aphrodisiac potential of C. bonduc root and lend support to the folkloric use as aphrodisiac.
MeSH term(s)	Animals ; Aphrodisiacs/pharmacology ; Caesalpinia ; Male ; Plant Extracts/pharmacology ; Rats ; Rats, Wistar ; Sexual Behavior, Animal
Chemical Substances	Aphrodisiacs ; Plant Extracts
Language	English
Publishing date	2021-04-23
Publishing country	Germany
Document type	Journal Article
ZDB-ID	7280-1
ISSN	1439-0272 ; 0303-4569
ISSN (online)	1439-0272
ISSN	0303-4569
DOI	10.1111/and.14072
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Article: Bone Marrow Adipose Tissue: To Be or Not To Be a Typical Adipose Tissue?

Hardouin, Pierre / Rharass, Tareck / Lucas, Stéphanie

Frontiers in endocrinology

2016 Volume 7, Page(s) 85

Abstract: Bone marrow adipose tissue (BMAT) emerges as a distinct fat depot whose importance has been proved in the bone-fat interaction. Indeed, it is well recognized that adipokines and free fatty acids released by adipocytes can directly or indirectly interfere ...

Abstract	Bone marrow adipose tissue (BMAT) emerges as a distinct fat depot whose importance has been proved in the bone-fat interaction. Indeed, it is well recognized that adipokines and free fatty acids released by adipocytes can directly or indirectly interfere with cells of bone remodeling or hematopoiesis. In pathological states, such as osteoporosis, each of adipose tissues - subcutaneous white adipose tissue (WAT), visceral WAT, brown adipose tissue (BAT), and BMAT - is differently associated with bone mineral density (BMD) variations. However, compared with the other fat depots, BMAT displays striking features that makes it a substantial actor in bone alterations. BMAT quantity is well associated with BMD loss in aging, menopause, and other metabolic conditions, such as anorexia nervosa. Consequently, BMAT is sensed as a relevant marker of a compromised bone integrity. However, analyses of BMAT development in metabolic diseases (obesity and diabetes) are scarce and should be, thus, more systematically addressed to better apprehend the bone modifications in that pathophysiological contexts. Moreover, bone marrow (BM) adipogenesis occurs throughout the whole life at different rates. Following an ordered spatiotemporal expansion, BMAT has turned to be a heterogeneous fat depot whose adipocytes diverge in their phenotype and their response to stimuli according to their location in bone and BM. In vitro, in vivo, and clinical studies point to a detrimental role of BM adipocytes (BMAs) throughout the release of paracrine factors that modulate osteoblast and/or osteoclast formation and function. However, the anatomical dissemination and the difficulties to access BMAs still hamper our understanding of the relative contribution of BMAT secretions compared with those of peripheral adipose tissues. A further characterization of the phenotype and the functional regulation of BMAs are ever more required. Based on currently available data and comparison with other fat tissues, this review addresses the originality of the BMAT with regard to its development, anatomy, metabolic properties, and response to physiological cues.
Language	English
Publishing date	2016
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2016.00085
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Article ; Online: Identification of the Axis β-Catenin-BTK in the Dynamic Adhesion of Chronic Lymphocytic Leukemia Cells to Their Microenvironment.

Mihoub, Imane / Rharass, Tareck / Ouriemmi, Souhaïl / Oudar, Antonin / Aubard, Laure / Gratio, Valérie / Lazarian, Gregory / Ferreira, Jordan / Dondi, Elisabetta / Cymbalista, Florence / Levy, Vincent / Baran-Marszak, Fanny / Varin-Blank, Nadine / Ledoux, Dominique / Le Roy, Christine / Gardano, Laura

International journal of molecular sciences

2023 Volume 24, Issue 24

Abstract: In the microenvironment, cell interactions are established between different cell types to regulate their migration, survival and activation. β-Catenin is a multifunctional protein that stabilizes cell-cell interactions and regulates cell survival ... ...

Abstract	In the microenvironment, cell interactions are established between different cell types to regulate their migration, survival and activation. β-Catenin is a multifunctional protein that stabilizes cell-cell interactions and regulates cell survival through its transcriptional activity. We used chronic lymphocytic leukemia (CLL) cells as a cellular model to study the role of β-catenin in regulating the adhesion of tumor cells to their microenvironment, which is necessary for tumor cell survival and accumulation. When co-cultured with a stromal cell line (HS-5), a fraction of the CLL cells adhere to stromal cells in a dynamic fashion regulated by the different levels of β-catenin expression. In non-adherent cells, β-catenin is stabilized in the cytosol and translocates into the nucleus, increasing the expression of cyclin D1. In adherent cells, the level of cytosolic β-catenin is low but membrane β-catenin helps to stabilize the adhesion of CLL to stromal cells. Indeed, the overexpression of β-catenin enhances the interaction of CLL with HS-5 cells, suggesting that this protein behaves as a regulator of cell adhesion to the stromal component and of the transcriptional regulation of cell survival. Inhibitors that block the stabilization of β-catenin alter this equilibrium and effectively disrupt the support that CLL cells receive from the cross-talk with the stroma.
MeSH term(s)	Humans ; beta Catenin/genetics ; beta Catenin/metabolism ; Cell Communication ; Cell Line, Tumor ; Leukemia, Lymphocytic, Chronic, B-Cell/pathology ; Stromal Cells/metabolism ; Tumor Microenvironment ; Agammaglobulinaemia Tyrosine Kinase/metabolism
Chemical Substances	beta Catenin ; Agammaglobulinaemia Tyrosine Kinase (EC 2.7.10.2)
Language	English
Publishing date	2023-12-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms242417623
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Article ; Online: Ascorbic acid alters cell fate commitment of human neural progenitors in a WNT/β-catenin/ROS signaling dependent manner.

Rharass, Tareck / Lantow, Margareta / Gbankoto, Adam / Weiss, Dieter G / Panáková, Daniela / Lucas, Stéphanie

Journal of biomedical science

2017 Volume 24, Issue 1, Page(s) 78

Abstract: Background: Improving the neuronal yield from in vitro cultivated neural progenitor cells (NPCs) is an essential challenge in transplantation therapy in neurological disorders. In this regard, Ascorbic acid (AA) is widely used to expand neurogenesis ... ...

Abstract	Background: Improving the neuronal yield from in vitro cultivated neural progenitor cells (NPCs) is an essential challenge in transplantation therapy in neurological disorders. In this regard, Ascorbic acid (AA) is widely used to expand neurogenesis from NPCs in cultures although the mechanisms of its action remain unclear. Neurogenesis from NPCs is regulated by the redox-sensitive WNT/β-catenin signaling pathway. We therefore aimed to investigate how AA interacts with this pathway and potentiates neurogenesis. Methods: Effects of 200 μM AA were compared with the pro-neurogenic reagent and WNT/β-catenin signaling agonist lithium chloride (LiCl), and molecules with antioxidant activities i.e. N-acetyl-L-cysteine (NAC) and ruthenium red (RuR), in differentiating neural progenitor ReNcell VM cells. Cells were supplemented with reagents for two periods of treatment: a full period encompassing the whole differentiation process versus an early short period that is restricted to the cell fate commitment stage. Intracellular redox balance and reactive oxygen species (ROS) metabolism were examined by flow cytometry using redox and ROS sensors. Confocal microscopy was performed to assess cell viability, neuronal yield, and levels of two proteins: Nucleoredoxin (NXN) and the WNT/β-catenin signaling component Dishevelled 2 (DVL2). TUBB3 and MYC gene responses were evaluated by quantitative real-time PCR. DVL2-NXN complex dissociation was measured by fluorescence resonance energy transfer (FRET). Results: In contrast to NAC which predictably exhibited an antioxidant effect, AA treatment enhanced ROS metabolism with no cytotoxic induction. Both drugs altered ROS levels only at the early stage of the differentiation as no changes were held beyond the neuronal fate commitment stage. FRET studies showed that AA treatment accelerated the redox-dependent release of the initial pool of DVL2 from its sequestration by NXN, while RuR treatment hampered the dissociation of the two proteins. Accordingly, AA increased WNT/β-catenin signaling output i.e. MYC mRNA level, whereas RuR attenuated it. Moreover, AA improved neurogenesis as much as LiCl as both TUBB3-positive cell yield and TUBB3 mRNA level increased, while NAC or RuR attenuated neurogenesis. Markedly, the neurogenesis outputs between the short and the full treatment with either NAC or AA were found unchanged, supporting our model that neuronal yield is altered by events taking place at the early phase of differentiation. Conclusions: Our findings demonstrate that AA treatment elevates ROS metabolism in a non-lethal manner prior to the NPCs commitment to their neuronal fate. Such effect stimulates the redox-sensitive DVL2 activation and WNT/β-catenin signaling response that would enhance the ensuing neuronal cell differentiation.
Language	English
Publishing date	2017-10-16
Publishing country	England
Document type	Journal Article
ZDB-ID	1193378-1
ISSN	1423-0127 ; 1021-7770
ISSN (online)	1423-0127
ISSN	1021-7770
DOI	10.1186/s12929-017-0385-1
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Article ; Online: Spatio-temporal model of endogenous ROS and raft-dependent WNT/beta-catenin signaling driving cell fate commitment in human neural progenitor cells.

Haack, Fiete / Lemcke, Heiko / Ewald, Roland / Rharass, Tareck / Uhrmacher, Adelinde M

PLoS computational biology

2015 Volume 11, Issue 3, Page(s) e1004106

Abstract: Canonical WNT/β-catenin signaling is a central pathway in embryonic development, but it is also connected to a number of cancers and developmental disorders. Here we apply a combined in-vitro and in-silico approach to investigate the spatio-temporal ... ...

Abstract	Canonical WNT/β-catenin signaling is a central pathway in embryonic development, but it is also connected to a number of cancers and developmental disorders. Here we apply a combined in-vitro and in-silico approach to investigate the spatio-temporal regulation of WNT/β-catenin signaling during the early neural differentiation process of human neural progenitors cells (hNPCs), which form a new prospect for replacement therapies in the context of neurodegenerative diseases. Experimental measurements indicate a second signal mechanism, in addition to canonical WNT signaling, being involved in the regulation of nuclear β-catenin levels during the cell fate commitment phase of neural differentiation. We find that the biphasic activation of β-catenin signaling observed experimentally can only be explained through a model that combines Reactive Oxygen Species (ROS) and raft dependent WNT/β-catenin signaling. Accordingly after initiation of differentiation endogenous ROS activates DVL in a redox-dependent manner leading to a transient activation of down-stream β-catenin signaling, followed by continuous auto/paracrine WNT signaling, which crucially depends on lipid rafts. Our simulation studies further illustrate the elaborate spatio-temporal regulation of DVL, which, depending on its concentration and localization, may either act as direct inducer of the transient ROS/β-catenin signal or as amplifier during continuous auto-/parcrine WNT/β-catenin signaling. In addition we provide the first stochastic computational model of WNT/β-catenin signaling that combines membrane-related and intracellular processes, including lipid rafts/receptor dynamics as well as WNT- and ROS-dependent β-catenin activation. The model's predictive ability is demonstrated under a wide range of varying conditions for in-vitro and in-silico reference data sets. Our in-silico approach is realized in a multi-level rule-based language, that facilitates the extension and modification of the model. Thus, our results provide both new insights and means to further our understanding of canonical WNT/β-catenin signaling and the role of ROS as intracellular signaling mediator.
MeSH term(s)	Cell Line ; Computational Biology ; Computer Simulation ; Humans ; Neural Stem Cells/metabolism ; Neural Stem Cells/physiology ; Reactive Oxygen Species/metabolism ; Reproducibility of Results ; Spatio-Temporal Analysis ; Wnt Proteins/metabolism ; Wnt Signaling Pathway/physiology ; beta Catenin/metabolism
Chemical Substances	Reactive Oxygen Species ; Wnt Proteins ; beta Catenin
Language	English
Publishing date	2015-03-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2193340-6
ISSN	1553-7358 ; 1553-734X
ISSN (online)	1553-7358
ISSN	1553-734X
DOI	10.1371/journal.pcbi.1004106
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Article ; Online: Ca2+-mediated mitochondrial reactive oxygen species metabolism augments Wnt/β-catenin pathway activation to facilitate cell differentiation.

Rharass, Tareck / Lemcke, Heiko / Lantow, Margareta / Kuznetsov, Sergei A / Weiss, Dieter G / Panáková, Daniela

The Journal of biological chemistry

2014 Volume 289, Issue 40, Page(s) 27937–27951

Abstract: Emerging evidence suggests that reactive oxygen species (ROS) can stimulate the Wnt/β-catenin pathway in a number of cellular processes. However, potential sources of endogenous ROS have not been thoroughly explored. Here, we show that growth factor ... ...

Abstract	Emerging evidence suggests that reactive oxygen species (ROS) can stimulate the Wnt/β-catenin pathway in a number of cellular processes. However, potential sources of endogenous ROS have not been thoroughly explored. Here, we show that growth factor depletion in human neural progenitor cells induces ROS production in mitochondria. Elevated ROS levels augment activation of Wnt/β-catenin signaling that regulates neural differentiation. We find that growth factor depletion stimulates the release of Ca(2+) from the endoplasmic reticulum stores. Ca(2+) subsequently accumulates in the mitochondria and triggers ROS production. The inhibition of mitochondrial Ca(2+) uptake with simultaneous growth factor depletion prevents the rise in ROS metabolism. Moreover, low ROS levels block the dissociation of the Wnt effector Dishevelled from nucleoredoxin. Attenuation of the response amplitudes of pathway effectors delays the onset of the Wnt/β-catenin pathway activation and results in markedly impaired neuronal differentiation. Our findings reveal Ca(2+)-mediated ROS metabolic cues that fine-tune the efficiency of cell differentiation by modulating the extent of the Wnt/β-catenin signaling output.
MeSH term(s)	Calcium/metabolism ; Cell Differentiation ; Humans ; Mitochondria/metabolism ; Neural Stem Cells/cytology ; Neural Stem Cells/metabolism ; Reactive Oxygen Species/metabolism ; Wnt Proteins/metabolism ; Wnt Signaling Pathway ; beta Catenin/genetics ; beta Catenin/metabolism
Chemical Substances	Reactive Oxygen Species ; Wnt Proteins ; beta Catenin ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2014-08-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M114.573519
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Article ; Online: Oxidative stress does not play a primary role in the toxicity induced with clinical doses of doxorubicin in myocardial H9c2 cells.

Rharass, Tareck / Gbankoto, Adam / Canal, Christophe / Kurşunluoğlu, Gizem / Bijoux, Amandine / Panáková, Daniela / Ribou, Anne-Cécile

Molecular and cellular biochemistry

2016 Volume 413, Issue 1-2, Page(s) 199–215

Abstract: The implication of oxidative stress as primary mechanism inducing doxorubicin (DOX) cardiotoxicity is still questionable as many in vitro studies implied supra-clinical drug doses or unreliable methodologies for reactive oxygen species (ROS) detection. ... ...

Abstract	The implication of oxidative stress as primary mechanism inducing doxorubicin (DOX) cardiotoxicity is still questionable as many in vitro studies implied supra-clinical drug doses or unreliable methodologies for reactive oxygen species (ROS) detection. The aim of this study was to clarify whether oxidative stress is involved in compliance with the conditions of clinical use of DOX, and using reliable tools for ROS detection. We examined the cytotoxic mechanisms of 2 μM DOX 1 day after the beginning of the treatment in differentiated H9c2 rat embryonic cardiac cells. Cells were exposed for 2 or 24 h with DOX to mimic a single chronic dosage or to favor accumulation, respectively. We found that apoptosis was prevalent in cells exposed for a short period with DOX: cells showed typical hallmarks as loss of anchorage ability, mitochondrial hyperpolarization followed by the collapse of mitochondrial activity, and nuclear condensation. Increasing the exposure period favored a shift to necrosis as the cells preferentially exhibited early DNA impairment and nuclear swelling. In either case, measuring the fluorescence lifetime of 1-pyrenebutyric acid or the intensities of dihydroethidium or amplex red showed a consistent pattern in ROS production which was a slight increased level far from representative of an oxidative stress. Moreover, pre-treatment with dexrazoxane provided a cytoprotective effect although it failed to detoxify ROS. Our data support that oxidative stress is unlikely to be the primary mechanism of DOX cardiac toxicity in vitro.
MeSH term(s)	Animals ; Antibiotics, Antineoplastic/toxicity ; Cell Line ; Dexrazoxane/pharmacology ; Dose-Response Relationship, Drug ; Doxorubicin/toxicity ; Myocytes, Cardiac/cytology ; Myocytes, Cardiac/drug effects ; Oxidative Stress/drug effects ; Rats ; Toxicity Tests
Chemical Substances	Antibiotics, Antineoplastic ; Dexrazoxane (048L81261F) ; Doxorubicin (80168379AG)
Language	English
Publishing date	2016-02
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	184833-1
ISSN	1573-4919 ; 0300-8177
ISSN (online)	1573-4919
ISSN	0300-8177
DOI	10.1007/s11010-016-2653-x
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Article: New method for the detection of reactive oxygen species in anti-tumoural activity of adriamycin: a comparison between hypoxic and normoxic cells.

Rharass, Tareck / Vigo, Jean / Salmon, Jean-Marie / Ribou, Anne-Cecile

Free radical research

2008 Volume 42, Issue 2, Page(s) 124–134

Abstract: Tumour hypoxia plays a role in chemoresistance in several human tumours. However, how hyperbaric oxygen leads to chemotherapeutic gain is unclear. This study investigates the relation of reactive oxygen species (ROS) generation with anti-tumoural effect ... ...

Abstract	Tumour hypoxia plays a role in chemoresistance in several human tumours. However, how hyperbaric oxygen leads to chemotherapeutic gain is unclear. This study investigates the relation of reactive oxygen species (ROS) generation with anti-tumoural effect of adriamycin (ADR) on CCRF-CEM cells under hypoxic (2% O(2)) and normoxic (21% O(2)) conditions. A new method was used to measure intracellular ROS variations through the fluorescence lifetime of 1-pyrenebutyric acid. At 24 h, ADR, probably via semiquinone radical, enhances ROS levels in normoxic cells compared to hypoxic cells. Long-term studies show that ROS are also generated by a second mechanism related to cell functions perturbation. ADR arrests the cell cycle progression both under hypoxia and normoxia, indicating that oxygen and ROS does not influence the DNA damaging activity of ADR. The findings reveal that moderate improvement of ADR cytotoxicity results from higher ROS formation in normoxic cells, leading to elevated induction of cell death.
MeSH term(s)	Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Cell Cycle/drug effects ; Cell Hypoxia/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Cytological Techniques ; DNA Damage/drug effects ; Doxorubicin/pharmacology ; Fluorescence ; Humans ; Oxygen/pharmacology ; Pyrenes/metabolism ; Reactive Oxygen Species/metabolism
Chemical Substances	Antineoplastic Agents ; Pyrenes ; Reactive Oxygen Species ; 1-pyrenebutyrate (3443-45-6) ; Doxorubicin (80168379AG) ; Oxygen (S88TT14065)
Language	English
Publishing date	2008-02
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1194130-3
ISSN	1029-2470 ; 1071-5762
ISSN (online)	1029-2470
ISSN	1071-5762
DOI	10.1080/10715760701834552
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