scholarly journals Plumbagin-induced oxidative stress leads to inhibition of Na+/K+-ATPase (NKA) in canine cancer cells

2019 ◽  
Author(s):  
Yousef Alharbi ◽  
Arvinder Kapur ◽  
Mildred Felder ◽  
Lisa Barroilhet ◽  
Timothy Stein ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cancer Cells ◽  
Oxygen Radicals ◽  
Outward Current ◽  
Radical Scavenger ◽  
Cancer Therapies ◽  
Drug Induced ◽  
Whole Cell Patch Clamp ◽  
Short Term Exposure ◽  
Canine Cancer

AbstractThe Na+/K+-ATPase (NKA) complex is the master regulator of membrane potential and a target for anti-cancer therapies. Here, we investigate the effect of drug-induced oxidative stress on NKA activity. The natural product, plumbagin increases oxygen radicals through inhibition of oxidative phosphorylation. As a result, plumbagin treatment results in decreased production of ATP and a rapid increase in intracellular oxygen radicals. We show that plumbagin induces apoptosis in canine cancer cells via oxidative stress. We use this model to test the effect of oxidative stress on NKA activity. Using whole-cell patch-clamp electrophysiology we demonstrate that short-term exposure (4 min) to plumbagin results in 48% decrease in outward current at +50 mV. Even when exogenous ATP was supplied to the cells, plumbagin treatment resulted in 46% inhibition outward current through NKA at +50 mV. In contrast, when the canine cancer cells were pre-treated with the oxygen radical scavenger, N-acetylcysteine, the NKA inhibitory activity of plumbagin was abrogated. These experiments demonstrate that the oxidative stress-causing agents such as plumbagin and its analogues, are a novel avenue to regulate NKA activity in tumors.

scholarly journals Control of Oxidative Stress in Cancer Chemoresistance: Spotlight on Nrf2 Role

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 510
Author(s):  
Giuseppina Barrera ◽  
Marie Angele Cucci ◽  
Margherita Grattarola ◽  
Chiara Dianzani ◽  
Giuliana Muzio ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Targeted Therapy ◽  
Cancer Cells ◽  
Antioxidant Response ◽  
Redox Status ◽  
Antioxidant Systems ◽  
Drug Induced ◽  
Transcriptional Coactivators ◽  
Metabolic Remodeling

Chemoresistance represents the main obstacle to cancer treatment with both conventional and targeted therapy. Beyond specific molecular alterations, which can lead to targeted therapy, metabolic remodeling, including the control of redox status, plays an important role in cancer cell survival following therapy. Although cancer cells generally have a high basal reactive oxygen species (ROS) level, which makes them more susceptible than normal cells to a further increase of ROS, chemoresistant cancer cells become highly adapted to intrinsic or drug-induced oxidative stress by upregulating their antioxidant systems. The antioxidant response is principally mediated by the transcription factor Nrf2, which has been considered the master regulator of antioxidant and cytoprotective genes. Nrf2 expression is often increased in several types of chemoresistant cancer cells, and its expression is mediated by diverse mechanisms. In addition to Nrf2, other transcription factors and transcriptional coactivators can participate to maintain the high antioxidant levels in chemo and radio-resistant cancer cells. The control of expression and function of these molecules has been recently deepened to identify which of these could be used as a new therapeutic target in the treatment of tumors resistant to conventional therapy. In this review, we report the more recent advances in the study of Nrf2 regulation in chemoresistant cancers and the role played by other transcription factors and transcriptional coactivators in the control of antioxidant responses in chemoresistant cancer cells.

scholarly journals New Developments in Photodynamic and Sonodynamic Cancer Therapy

2018 ◽  
Vol 4 (Supplement 2) ◽  
pp. 222s-222s
Author(s):  
M. Weber
Keyword(s):  
Cancer Therapy ◽  
Cancer Cells ◽  
Oxygen Radicals ◽  
Low Level Laser Therapy ◽  
Cancer Therapies ◽  
Treatment Protocols ◽  
New Developments ◽  
Level Laser ◽  
Photosensitizing Agents ◽  
Technological Developments

Background: Photodynamic therapy (PDT) is already widely used for the treatment of superficial tumors. Due to technological developments in the field of low-level laser therapy it can now also be used to treat various kinds of internal cancers, including breast, lung, prostate, bladder, rectal and other cancers. The principle is the photoactivation of a light sensitive substance (photosensitizer) which is injected into the bloodstream or directly into the tumor. After a certain amount of time the photosensitizer will be taken up by cancer cells by endocytosis. The cancerous area is then irradiated by laser light of appropriate wavelength, according to the absorption spectra of the photosensitizer. The emitted photons are absorbed by the photosensitizer which is thereby shifted to a highly reactive state. As a consequent, it interacts with tissue oxygen, leading to the development of reactive singlet oxygen radicals which are cytotoxic for cancer cells. Additional sonodynamic cancer therapy (SDT) improves the clinical outcomes. Aim: We describe a broad number of case studies to demonstrate the outstanding potential of the treatment protocols. Methods: We used indocyanine green, curcumin and hypericin as photosensitizing agents. Upon light activation, the agents react with oxygen, leading to the development of oxygen radicals which induce irreparable damage on cancer cells. Results: In the vast majority of all cases, significant reductions of tumor mass up to complete remissions could be achieved. Conclusion: Protocols consisting of photodynamic and sonodynamic cancer therapies have the potential to become mainstream cancer therapies in the next couple of years.

scholarly journals Drug-Induced Oxidative Stress and Toxicity

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Damian G. Deavall ◽  
Elizabeth A. Martin ◽  
Judith M. Horner ◽  
Ruth Roberts
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Oxygen Radicals ◽  
Oxygen Species ◽  
Cardiac Damage ◽  
Drug Induced ◽  
Cellular Targets ◽  
Disease States ◽  
Normal Metabolism ◽  
Cellular Components

Reactive oxygen species (ROS) are a byproduct of normal metabolism and have roles in cell signaling and homeostasis. Species include oxygen radicals and reactive nonradicals. Mechanisms exist that regulate cellular levels of ROS, as their reactive nature may otherwise cause damage to key cellular components including DNA, protein, and lipid. When the cellular antioxidant capacity is exceeded, oxidative stress can result. Pleiotropic deleterious effects of oxidative stress are observed in numerous disease states and are also implicated in a variety of drug-induced toxicities. In this paper, we examine the nature of ROS-induced damage on key cellular targets of oxidative stress. We also review evidence implicating ROS in clinically relevant, drug-related side effects including doxorubicin-induced cardiac damage, azidothymidine-induced myopathy, and cisplatin-induced ototoxicity.

scholarly journals Plumbagin-induced oxidative stress leads to inhibition of Na+/K+-ATPase (NKA) in canine cancer cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yousef Alharbi ◽  
Arvinder Kapur ◽  
Mildred Felder ◽  
Lisa Barroilhet ◽  
Timothy Stein ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cancer Cells ◽  
Canine Cancer

scholarly journals PERK signaling through C/EBPδ contributes to ER stress-induced expression of immunomodulatory and tumor promoting chemokines by cancer cells

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Namratha Sheshadri ◽  
Dipak K. Poria ◽  
Shikha Sharan ◽  
Ying Hu ◽  
Chunhua Yan ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Er Stress ◽  
Cancer Cells ◽  
Transcriptional Profiling ◽  
Tumor Biology ◽  
Breast Cancer Cell Lines ◽  
Cancer Therapies ◽  
Global Protein Synthesis ◽  
Short Term Exposure ◽  
Factor C

AbstractCancer cells experience endoplasmic reticulum (ER) stress due to activated oncogenes and conditions of nutrient deprivation and hypoxia. The ensuing unfolded protein response (UPR) is executed by ATF6, IRE1 and PERK pathways. Adaptation to mild ER stress promotes tumor cell survival and aggressiveness. Unmitigated ER stress, however, will result in cell death and is a potential avenue for cancer therapies. Because of this yin-yang nature of ER stress, it is imperative that we fully understand the mechanisms and dynamics of the UPR and its contribution to the complexity of tumor biology. The PERK pathway inhibits global protein synthesis while allowing translation of specific mRNAs, such as the ATF4 transcription factor. Using thapsigargin and tunicamycin to induce acute ER stress, we identified the transcription factor C/EBPδ (CEBPD) as a mediator of PERK signaling to secretion of tumor promoting chemokines. In melanoma and breast cancer cell lines, PERK mediated early induction of C/EBPδ through ATF4-independent pathways that involved at least in part Janus kinases and the STAT3 transcription factor. Transcriptional profiling revealed that C/EBPδ contributed to 20% of thapsigargin response genes including chaperones, components of ER-associated degradation, and apoptosis inhibitors. In addition, C/EBPδ supported the expression of the chemokines CXCL8 (IL-8) and CCL20, which are known for their tumor promoting and immunosuppressive properties. With a paradigm of short-term exposure to thapsigargin, which was sufficient to trigger prolonged activation of the UPR in cancer cells, we found that conditioned media from such cells induced cytokine expression in myeloid cells. In addition, activation of the CXCL8 receptor CXCR1 during thapsigargin exposure supported subsequent sphere formation by cancer cells. Taken together, these investigations elucidated a novel mechanism of ER stress-induced transmissible signals in tumor cells that may be particularly relevant in the context of pharmacological interventions.

scholarly journals ZnO Nanoparticles: A Promising Anticancer Agent

10.5772/63437 ◽  
2016 ◽  
Vol 3 ◽  
pp. 9 ◽  
Author(s):  
Gunjan Bisht ◽  
Sagar Rayamajhi
Keyword(s):  
Oxidative Stress ◽  
Cancer Cells ◽  
Zno Nanoparticles ◽  
Cell Cycle Progression ◽  
Anticancer Agent ◽  
Zinc Concentration ◽  
Cancer Therapies ◽  
Protein Activity ◽  
High Zinc ◽  
High Zinc Concentration

Nanoparticles, with their selective targeting capabilities and superior efficacy, are becoming increasingly important in modern cancer therapy and starting to overshadow traditional cancer therapies such as chemotherapy radiation and surgery. ZnO nanoparticles, with their unique properties such as biocompatibility, high selectivity, enhanced cytotoxicity and easy synthesis, may be a promising anticancer agent. Zinc, as one of the major trace elements of the human body and co-factor of more than 300 mammalian enzymes, plays an important role in maintaining crucial cellular processes including oxidative stress, DNA replication, DNA repair, cell cycle progression and apoptosis. Thus, it is evident that an alteration in zinc levels in cancer cells can cause a deleterious effect. Research has shown that low zinc concentration in cells leads to the initiation and progression of cancer and high zinc concentration shows toxic effects. Zinc-mediated protein activity disequilibrium and oxidative stress through reactive oxygen species (ROS) may be the probable mechanism of this cytotoxic effect. The selective localization of ZnO nanoparticles towards cancer cells due to enhanced permeability and retention (EPR) effect and electrostatic interaction and selective cytotoxicity due to increased ROS present in cancer cells show that ZnO nanoparticles can selectively target and kill cancer cells, making them a promising anticancer agent.

792: Role of Oxidative Stress in Tumorigenic Potential of Bladder Cancer Cells

2005 ◽  
Vol 173 (4S) ◽  
pp. 214-215 ◽  
Author(s):  
Daniel Cho ◽  
Xiao Fang Ha ◽  
J. Andre Melendez ◽  
Louis J. Giorgi ◽  
Badar M. Mian
Keyword(s):  
Oxidative Stress ◽  
Bladder Cancer ◽  
Cancer Cells ◽  
Tumorigenic Potential ◽  
Bladder Cancer Cells

The Dinitrophenol and Potassium Iodate Influence on Hordeum Vulgare Seedlings Viability\

2018 ◽  
Vol 69 (8) ◽  
pp. 2160-2166
Author(s):  
Elena Todirascu Ciornea ◽  
Gabriela Dumitru ◽  
Ion Sandu
Keyword(s):  
Oxidative Stress ◽  
Hordeum Vulgare ◽  
Antioxidant Enzyme ◽  
Oxygen Radicals ◽  
Free Oxygen Radicals ◽  
Potassium Iodate ◽  
Free Oxygen ◽  
Oxidative Stress Enzymes ◽  
Stress Enzymes ◽  
Seeds Germination

The using of the pesticides of dinitrophenol type in agriculture has as consequence the major pollution of the environment, the plants taking these substances from the soil and once with these ones they reach in the human and animal organism where they product disequilibrium that are interpreted through the accumulation of free oxygen radicals with direct repercussions on the antioxidant enzyme�s synthesis intensification and on their activity�s increase. The apply of treatments on the barley seeds had significant effects regarding the seeds� germination, the young plants� growth, the oxidative stress enzymes� activity, but also regarding the content of photoassimilators and carotenoids pigments.

Non-canonical Functions of Telomerase Reverse Transcriptase: Emerging Roles and Biological Relevance

2020 ◽  
Vol 20 (6) ◽  
pp. 498-507 ◽  
Author(s):  
Connor A.H. Thompson ◽  
Judy M.Y. Wong
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Reverse Transcriptase ◽  
Cancer Cells ◽  
Telomere Length ◽  
Telomere Maintenance ◽  
Telomerase Reverse Transcriptase ◽  
Alternative Mechanism ◽  
Dependent Manner ◽  
Mitochondrial Integrity

Increasing evidence from research on telomerase suggests that in addition to its catalytic telomere repeat synthesis activity, telomerase may have other biologically important functions. The canonical roles of telomerase are at the telomere ends where they elongate telomeres and maintain genomic stability and cellular lifespan. The catalytic protein component Telomerase Reverse Transcriptase (TERT) is preferentially expressed at high levels in cancer cells despite the existence of an alternative mechanism for telomere maintenance (alternative lengthening of telomeres or ALT). TERT is also expressed at higher levels than necessary for maintaining functional telomere length, suggesting other possible adaptive functions. Emerging non-canonical roles of TERT include regulation of non-telomeric DNA damage responses, promotion of cell growth and proliferation, acceleration of cell cycle kinetics, and control of mitochondrial integrity following oxidative stress. Non-canonical activities of TERT primarily show cellular protective effects, and nuclear TERT has been shown to protect against cell death following double-stranded DNA damage, independent of its role in telomere length maintenance. TERT has been suggested to act as a chromatin modulator and participate in the transcriptional regulation of gene expression. TERT has also been reported to regulate transcript levels through an RNA-dependent RNA Polymerase (RdRP) activity and produce siRNAs in a Dicer-dependent manner. At the mitochondria, TERT is suggested to protect against oxidative stress-induced mtDNA damage and promote mitochondrial integrity. These extra-telomeric functions of TERT may be advantageous in the context of increased proliferation and metabolic stress often found in rapidly-dividing cancer cells. Understanding the spectrum of non-canonical functions of telomerase may have important implications for the rational design of anti-cancer chemotherapeutic drugs.

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