Suppression of Reactive Oxygen Species and Enhanced Stress Tolerance in Rubia cordifolia Cells Expressing the rolC Oncogene

It is known that expression of the Agrobacterium rhizogenes rolC gene in transformed plant cells causes defense-like reactions, such as increased phytoalexin production and expression of pathogenesis-related proteins. In the present study, we examined whether this phenomenon is associated with increased production of reactive oxygen species (ROS). Single-cell assays based on confocal microscopy and fluorogenic dyes (2,7-dichlorofluorescein diacetate and dihydrorhodamine 123) showed reduced steady-state levels of ROS in rolC-expressing Rubia cordifolia cells as compared with normal cells. Paraquat, a ROS inducer, caused significant ROS elevation in normal cells but had little effect on rolC-transformed cells. Likewise, ROS elevation triggered by a light stress was suppressed in transformed cells. Our results indicate that the rolC gene acts as a ROS suppressor in unstressed cells and its expression prevents stress-induced ROS elevations. We detected a two- to threefold increase in tolerance of rolC-transformed cells to salt, heat, and cold treatments. Simultaneously, rolC-transformed cells maintained permanently active defensive status, as found by measuring isochorismate synthase gene expression and anthraquinone production. Thus, the oncogene provoked multiple effects in which ROS production and phytoalexin production were clearly dissociated.

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Role of reactive oxygen species for apoptosis of transformed cells induced by TGF-β-treated normal cells

Journal of Cancer Research and Clinical Oncology ◽

10.1007/bf02572078 ◽

1995 ◽

Vol 121 (S1) ◽

pp. A29-A29

Author(s):

J. M. Jürgensmeier ◽

C. Langer ◽

G. Bauer

Keyword(s):

Reactive Oxygen Species ◽

Reactive Oxygen ◽

Transformed Cells ◽

Oxygen Species ◽

Normal Cells

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Reactive Oxygen Species Act at both TGF-β-Dependent and -Independent Steps during Induction of Apoptosis of Transformed Cells by Normal Cells

Experimental Cell Research ◽

10.1006/excr.1996.0015 ◽

1996 ◽

Vol 222 (1) ◽

pp. 117-124 ◽

Cited By ~ 48

Author(s):

Christiane Langer ◽

Juliane M. Jürgensmeier ◽

Georg Bauer

Keyword(s):

Reactive Oxygen Species ◽

Reactive Oxygen ◽

Transformed Cells ◽

Oxygen Species ◽

Normal Cells ◽

Induction Of Apoptosis

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The Role of Reactive Oxygen Species in Tumor Treatment and its Impact on Bone Marrow Hematopoiesis

Current Drug Targets ◽

10.2174/1389450120666191021110208 ◽

2020 ◽

Vol 21 (5) ◽

pp. 477-498

Author(s):

Yongfeng Chen ◽

Xingjing Luo ◽

Zhenyou Zou ◽

Yong Liang

Keyword(s):

Reactive Oxygen Species ◽

Bone Marrow ◽

Oxidative Damage ◽

Tumor Cells ◽

Reactive Oxygen ◽

Oxygen Species ◽

Tumor Treatment ◽

Normal Cells ◽

Treatment And Prevention

Reactive oxygen species (ROS), an important molecule inducing oxidative stress in organisms, play a key role in tumorigenesis, tumor progression and recurrence. Recent findings on ROS have shown that ROS can be used to treat cancer as they accelerate the death of tumor cells. At present, pro-oxidant drugs that are intended to increase ROS levels of the tumor cells have been widely used in the clinic. However, ROS are a double-edged sword in the treatment of tumors. High levels of ROS induce not only the death of tumor cells but also oxidative damage to normal cells, especially bone marrow hemopoietic cells, which leads to bone marrow suppression and (or) other side effects, weak efficacy of tumor treatment and even threatening patients’ life. How to enhance the killing effect of ROS on tumor cells while avoiding oxidative damage to the normal cells has become an urgent issue. This study is a review of the latest progress in the role of ROS-mediated programmed death in tumor treatment and prevention and treatment of oxidative damage in bone marrow induced by ROS.

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3-Bromopyruvate potentiates TRAIL-induced apoptosis in human colon cancer cells through a reactive oxygen species- and caspase-dependent mitochondrial pathway

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2019-0131 ◽

2019 ◽

Vol 97 (12) ◽

pp. 1176-1184 ◽

Cited By ~ 3

Author(s):

Hassan Abbaszadeh ◽

Armita Valizadeh ◽

Masoud Mahdavinia ◽

Ali Teimoori ◽

Mohammad Hassan Pipelzadeh ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Colon Cancer ◽

Cancer Cells ◽

Reactive Oxygen ◽

Human Colon ◽

Inhibitory Effect ◽

Oxygen Species ◽

Colon Cancer Cells ◽

Human Colon Cancer ◽

Normal Cells

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a promising anticancer cytokine with minimal toxicity towards normal cells. Nevertheless, most primary cancers are often intrinsically TRAIL-resistant or can acquire resistance after TRAIL therapy. This study aimed to investigate the inhibitory effect of co-treatment of 3-bromopyruvate (3-BP) as a potent anticancer agent with TRAIL on colon cancer cells (HT-29). The results of present study indicated that combined treatment with 3-BP and TRAIL inhibited the proliferation of HT-29 cells to a greater extent (88.4%) compared with 3-BP (54%) or TRAIL (11%) treatment alone. In contrast, the combination of 3-BP and TRAIL had no significant inhibitory effect on the proliferation of normal cells (HEK-293) (8.4%). At a cellular mechanistic level, the present study showed that 3-BP sensitized human colon cancer cells to TRAIL-induced apoptosis via reactive oxygen species generation, upregulation of Bax, downregulation of Bcl-2 and survivin, release of cytochrome c into the cytosol, and activation of caspase-3. In normal cells, 3-BP, TRAIL, or combination of both had no significant effect on the reactive oxygen species levels, release of cytochrome c, and caspase-3 activity. Therefore, the combination of 3-BP and TRAIL can be a promising therapeutic strategy for treatment of colon cancer.

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The study of intracellular reactive oxygen species and mitochondrial membrane potential in normal cells exposed to diagnostic X ray

2015 4th International Conference on Instrumentation, Communications, Information Technology, and Biomedical Engineering (ICICI-BME) ◽

10.1109/icici-bme.2015.7401370 ◽

2015 ◽

Author(s):

Montree Tungjai ◽

Jiraporn Kantapan ◽

Yutthana Bunmakat ◽

Suchart Kothan

Keyword(s):

Reactive Oxygen Species ◽

Membrane Potential ◽

Mitochondrial Membrane Potential ◽

Mitochondrial Membrane ◽

Reactive Oxygen ◽

Intracellular Reactive Oxygen Species ◽

Oxygen Species ◽

Normal Cells ◽

X Ray

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Reactive Oxygen Species-Responsive Miktoarm Amphiphile for Triggered Intracellular Release of Anti-Cancer Therapeutics

Polymers ◽

10.3390/polym13244418 ◽

2021 ◽

Vol 13 (24) ◽

pp. 4418

Author(s):

Hyun-Chul Kim ◽

Eunjoo Kim ◽

Se Guen Lee ◽

Sung Jun Lee ◽

Sang Won Jeong ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Reactive Oxygen ◽

Cancer Therapeutics ◽

In Vitro Cytotoxicity ◽

Oxygen Species ◽

Normal Cells ◽

Research Attention ◽

Hek 293 ◽

Release Device

Reactive oxygen species (ROS)-responsive nanocarriers have received considerable research attention as putative cancer treatments because their tumor cell targets have high ROS levels. Here, we synthesized a miktoarm amphiphile of dithioketal-linked ditocopheryl polyethylene glycol (DTTP) by introducing ROS-cleavable thioketal groups as linkers between the hydrophilic and hydrophobic moieties. We used the product as a carrier for the controlled release of doxorubicin (DOX). DTTP has a critical micelle concentration (CMC) as low as 1.55 μg/mL (4.18 × 10−4 mM), encapsulation efficiency as high as 43.6 ± 0.23% and 14.6 nm particle size. The DTTP micelles were very responsive to ROS and released their DOX loads in a controlled manner. The tocopheryl derivates linked to DTTP generated ROS and added to the intracellular ROS in MCF-7 cancer cells but not in HEK-293 normal cells. In vitro cytotoxicity assays demonstrated that DOX-encapsulated DTTP micelles displayed strong antitumor activity but only slightly increased apoptosis in normal cells. This ROS-triggered, self-accelerating drug release device has high therapeutic efficacy and could be a practical new strategy for the clinical application of ROS-responsive drug delivery systems.

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Reactive Oxygen Species Are Differentially Regulated in Chronic Myeloid Leukemia Versus Philadelphia Negative Myeloproliferative Neoplasms

Blood ◽

10.1182/blood.v112.11.4215.4215 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4215-4215

Author(s):

Estelle Guerin ◽

Francis Belloc ◽

Gabriel Etienne ◽

Pierre Duffau ◽

Francois-Xavier Mahon ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Bone Marrow ◽

Peripheral Blood ◽

Myeloproliferative Neoplasms ◽

Reactive Oxygen ◽

Ros Generation ◽

Separate Analysis ◽

Ros Production ◽

Oxygen Species ◽

Normal Cells

Abstract Deregulation of tyrosine-kinases is a characteristic of most Myeloproliferative Neoplasms (MPN); evolution from chronic phase to acute leukemia depends on the acquisition of additional mutations. Reactive Oxygen Species (ROS), the production of which is increased by tyrosine-kinase activation, can be responsible for additional mutations. The role of ROS in generating genetic aberrations has been mainly studied in BCR-ABL-positive cell lines. Little is known of ROS metabolism in primary cells from CML or Philadelphia-negative MPN (Ph-MPN). After informed consent, cells from blood or bone marrow were obtained from patients diagnosed with CML (12 bone marrow (BM), 8 peripheral blood (PB)), or Ph-MPN (4 Polycythemia Vera, 6 Essential Thrombocythemia, 3 Primary Myelofibroses, 2 atypical CML) and from healthy donors (bone marrow donors) or patients devoid of hematological disease undergoing thoracotomy. Cells were incubated with DCFDA, a fluorogenic marker of ROS production, labelled with an anti-CD45 antibody, stimulated with either the oxidant hydrogen peroxide (H2O2) or the PKC activator Phorbol Myristate Acetate (PMA), and analysed for ROS production by flow cytometry. CD45/SSC gating allowed separate analysis of granulocytes, monocytes or lymphocytes. The basal level of ROS was not higher in CML cells as compared to normal BM or PB leukocytes. It was even significantly lower in CML lymphocytes, either from the BM (2.35 Arbitrary Units vs 8.3 AU, p=5.5 10−5) or PB (2.47 AU vs 7.4 AU, p=3.10−5) and in CML granulocytes from peripheral blood (14 AU vs 45 AU, p =10 −5), but not bone marrow. The ROS levels of Ph-MPN cells were similar or slightly higher than control cells. Upon H2O2 stimulation however, ROS production increased significantly more in CML cells as compared to normal cells (6 fold increase), whatever the cell type (granulocytes, monocytes and lymphocytes) or their origin (PB or BM). In contrast, for Ph-MPN cells, H2O2-stimulated ROS production was close to that of normal cells, with only BM lymphocytes showing ROS generation four fold higher than control BM lymphocytes. After PMA stimulation, which yielded a more modest ROS production than H2O2, CML cells behaved similarly to normal cells, whereas ROS production was four fold higher in Ph-MPN cells, whatever their type and origin. In conclusion, ROS levels at the basal stage are not higher in MPN cells, whether they are Philadelphia positive or negative, as compared to normal cells. Various kinds of stimulation induce different patterns of response, CML cells being more sensitive to oxidants whereas Ph-MPN cells respond more to the cytokine-mimicking agent PMA. These results suggest that the mechanisms of ROS generation and thus of genetic instability are different in CML and Ph-MPN.

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Lanthanum-Containing Magnesium Alloy with Antitumor Function Based on Increased Reactive Oxygen Species

Applied Sciences ◽

10.3390/app8112109 ◽

2018 ◽

Vol 8 (11) ◽

pp. 2109 ◽

Cited By ~ 5

Author(s):

Cijun Shuai ◽

Long Liu ◽

Youwen Yang ◽

Chengde Gao ◽

Mingchun Zhao ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Tumor Cell ◽

Bone Tumor ◽

Reactive Oxygen ◽

Species Level ◽

Reactive Oxygen Species Level ◽

Oxygen Species ◽

High Cell ◽

Tumor Cell Death ◽

Normal Cells

Developing antitumor implants is of great significance to repair tumor-induced bone defects and simultaneously prevent bone tumor recurrence. The tumor cells, compared to normal cells, have a high reactive oxygen species level. They are vulnerable to oxidative insults under increased intrinsic oxidative stress. The lanthanum (La) ion with high phospholipid binding ability can open the mitochondrial permeability transition pore, which blocks the electron transport chain in the mitochondria, and consequently increases reactive oxygen species level. In this study, La was alloyed to Mg-6Zn-0.5Zr (ZK60) through selective laser melting technology. The results indicated that the mitochondrial membrane potential dropped whilst the reactive oxygen species increased as the La content increased. ZK60-1.0La revealed a high cell inhibition rate of 61.9% for bone tumor cell and high cell viability of 91.9% for normal cells, indicating that the alloy could induce bone tumor cell death, as well as exhibit good biocompatibility for normal cell. In addition, its degradation rate 1.23 mm/year was lower than that of ZK60 alloy 2.13 mm/year, which was mainly attributed to the grain refinement.

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