scholarly journals Sestrins as a Therapeutic Bridge between ROS and Autophagy in Cancer

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1415 ◽  
Author(s):  
Sánchez-Álvarez ◽  
Strippoli ◽  
Donadelli ◽  
Bazhin ◽  
Cordani
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Personalized Medicine ◽  
Cancer Cells ◽  
Cell Metabolism ◽  
Tumor Therapy ◽  
Nutrient Sensing ◽  
Metabolic Adaptation ◽  
Pharmacological Intervention ◽  
Oxygen Species

: The regulation of Reactive Oxygen Species (ROS) levels and the contribution therein from networks regulating cell metabolism, such as autophagy and the mTOR-dependent nutrient-sensing pathway, constitute major targets for selective therapeutic intervention against several types of tumors, due to their extensive rewiring in cancer cells as compared to healthy cells. Here, we discuss the sestrin family of proteins—homeostatic transducers of oxidative stress, and drivers of antioxidant and metabolic adaptation—as emerging targets for pharmacological intervention. These adaptive regulators lie at the intersection of those two priority nodes of interest in antitumor intervention—ROS control and the regulation of cell metabolism and autophagy—therefore, they hold the potential not only for the development of completely novel compounds, but also for leveraging on synergistic strategies with current options for tumor therapy and classification/stadiation to achieve personalized medicine.

scholarly journals BA6 Induces Apoptosis via Stimulation of Reactive Oxygen Species and Inhibition of Oxidative Phosphorylation in Human Lung Cancer Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-21 ◽  
Author(s):  
Meng-Hsuan Cheng ◽  
Hung-Ling Huang ◽  
Yen-You Lin ◽  
Kuan-Hao Tsui ◽  
Pei-Chin Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lung Cancer ◽  
Reactive Oxygen Species ◽  
Cancer Cells ◽  
Human Lung ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Oxygen Species ◽  
Apoptotic Pathway ◽  
Induced Apoptosis

Lung cancer is the leading cause of cancer deaths in the world, with a five-year survival rate of less than 30%. Clinically effective chemotherapeutic treatments at the initial stage may eventually face the dilemma of no drug being effective due to drug resistance; therefore, finding new effective drugs for lung cancer treatment is a necessary and important issue. Compounds capable of further increasing the oxidative stress of cancer cells are considered to have anticancer potential because they possessed the ability to induce apoptosis. This study mainly investigated the effects of BA6 (heteronemin), the marine sponge sesterterpene, on lung cancer cell apoptosis, via modulation of mitochondrial reactive oxygen species (mtROS) and oxidative phosphorylation (OXPHOS). BA6 has cellular cytotoxic activities against a variety of cancer cell lines, but it has no effect on nontumor cells. The BA6-treated lung cancer cells show a significant increase in both cellular ROS and mtROS, which in turn caused the loss of mitochondrial membrane potential (MMP). The increase of oxidative stress in lung cancer cells treated with BA6 was accompanied by a decrease in the expression of antioxidant enzymes Cu/Zn SOD, MnSOD, and catalase. In addition, OXPHOS performed in the mitochondria and glycolysis in the cytoplasm were inhibited, which subsequently reduced downstream ATP production. Pretreatment with mitochondria-targeted antioxidant MitoTEMPO reduced BA6-induced apoptosis through the mitochondria-dependent apoptotic pathway, which was accompanied by increased cell viability, decreased mtROS, enhanced MMP, and suppressed expression of cleaved caspase-3 and caspase-9 proteins. In conclusion, the results of this study clarify the mechanism of BA6-induced apoptosis in lung cancer cells via the mitochondrial apoptotic pathway, suggesting that it is a potentially innovative alternative to the treatment of human lung cancer.

scholarly journals Protocatechuic Acid, a Simple Plant Secondary Metabolite, Induced Apoptosis by Promoting Oxidative Stress through HO-1 Downregulation and p21 Upregulation in Colon Cancer Cells

Biomolecules ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1485
Author(s):  
Rosaria Acquaviva ◽  
Barbara Tomasello ◽  
Claudia Di Giacomo ◽  
Rosa Santangelo ◽  
Alfonsina La Mantia ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Reactive Oxygen Species ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Protocatechuic Acid ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Colon Cancer Cells ◽  
Glutamylcysteine Synthetase

Gastrointestinal cancers, particularly colorectal cancer, are mainly influenced by the dietary factor. A diet rich in fruits and vegetables can help to reduce the incidence of colorectal cancer thanks to the phenolic compounds, which possess antimutagenic and anticarcinogenic properties. Polyphenols, alongside their well-known antioxidant properties, also show a pro-oxidative potential, which makes it possible to sensitize tumor cells to oxidative stress. HO-1 combined with antioxidant activity, when overexpressed in cancer cells, is involved in tumor progression, and its inhibition is considered a feasible therapeutic strategy in cancer treatment. In this study, the effects of protocatechuic acid (PCA) on the viability of colon cancer cells (CaCo-2), annexin V, LDH release, reactive oxygen species levels, total thiol content, HO-1, γ-glutamylcysteine synthetase, and p21 expression were evaluated. PCA induced, in a dose-dependent manner, a significantly reduced cell viability of CaCo-2 by oxidative/antioxidant imbalance. The phenolic acid induced modifications in levels of HO-1, non-proteic thiol groups, γ-glutamylcysteine synthetase, reactive oxygen species, and p21. PCA induced a pro-oxidant effect in cancer cells, and the in vitro pro-apoptotic effect on CaCo-2 cells is mediated by the modulation of redox balance and the inhibition of the HO-1 system that led to the activation of p21. Our results suggest that PCA may represent a useful tool in prevention and/or therapy of colon cancer.

scholarly journals Reactive Oxygen Species, Metabolic Plasticity, and Drug Resistance in Cancer

2020 ◽  
Vol 21 (10) ◽  
pp. 3412 ◽  
Author(s):  
Vikas Bhardwaj ◽  
Jun He
Keyword(s):  
Reactive Oxygen Species ◽  
Cancer Cells ◽  
Reactive Oxygen ◽  
Tca Cycle ◽  
Metabolic Adaptation ◽  
Oxygen Species ◽  
Metabolic Plasticity ◽  
The Tca Cycle ◽  
Clinical Benefits ◽  
High Level

The metabolic abnormality observed in tumors is characterized by the dependence of cancer cells on glycolysis for their energy requirements. Cancer cells also exhibit a high level of reactive oxygen species (ROS), largely due to the alteration of cellular bioenergetics. A highly coordinated interplay between tumor energetics and ROS generates a powerful phenotype that provides the tumor cells with proliferative, antiapoptotic, and overall aggressive characteristics. In this review article, we summarize the literature on how ROS impacts energy metabolism by regulating key metabolic enzymes and how metabolic pathways e.g., glycolysis, PPP, and the TCA cycle reciprocally affect the generation and maintenance of ROS homeostasis. Lastly, we discuss how metabolic adaptation in cancer influences the tumor’s response to chemotherapeutic drugs. Though attempts of targeting tumor energetics have shown promising preclinical outcomes, the clinical benefits are yet to be fully achieved. A better understanding of the interaction between metabolic abnormalities and involvement of ROS under the chemo-induced stress will help develop new strategies and personalized approaches to improve the therapeutic efficiency in cancer patients.

scholarly journals Anti-cancer agents and reactive oxygen species modulators that target cancer cell metabolism

2017 ◽  
Vol 89 (9) ◽  
pp. 1333-1348
Author(s):  
Fidelis Toloyi Ndombera
Keyword(s):  
Reactive Oxygen Species ◽  
Cancer Cells ◽  
Cell Metabolism ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Functional Studies ◽  
Anti Cancer ◽  
Cancer Cell Metabolism ◽  
Protective Threshold ◽  
Target Cancer

AbstractTraditionally the perspective on reactive oxygen species (ROS) has centered on the role they play as carcinogenic or cancer-causing radicals. Over the years, characterization and functional studies have revealed the complexity of ROS as signaling molecules that regulate various physiological cellular responses or whose levels are altered in various diseases. Cancer cells often maintain high basal level of ROS and are vulnerable to any further increase in ROS levels beyond a certain protective threshold. Consequently, ROS-modulation has emerged as an anticancer strategy with synthesis of various ROS-inducing or responsive agents that target cancer cells. Of note, an increased carbohydrate uptake and/or induction of death receptors of cancer cells was exploited to develop glycoconjugates that potentially induce cellular stress, ROS and apoptosis. This mini review highlights the development of compounds that target cancer cells by taking advantage of redox or metabolic alteration in cancer cells.

scholarly journals Positive feedback between ROS and cis-axis of PIASxα/p38α-SUMOylation/MK2 facilitates gastric cancer metastasis

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Qian Wang ◽  
Ci Xu ◽  
Qiang Fan ◽  
Haihua Yuan ◽  
Xin Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gastric Cancer ◽  
Reactive Oxygen Species ◽  
Stress Response ◽  
Cancer Cells ◽  
Regulatory Mechanism ◽  
Reactive Oxygen ◽  
Oxidative Stress Response ◽  
Oxygen Species ◽  
Gastric Cancer Cells

AbstractMAPK/p38 is an important mammalian signaling cascade that responds to a variety of intracellular or extracellular stimuli, such as reactive oxygen species (ROS), and participates in numerous physiological and pathological processes. However, the biological function of p38 in different tumors, and even at different stages of the same tumor, remains elusive. To further understand the regulatory mechanism of p38 and oxidative stress in the occurrence and development of gastric cancer, we report SUMOylation as a novel post-translational modification occurring on lysine 152 of MAPK14/p38α through immunoprecipitation and series of pull-down assays in vitro and in vivo. Importantly, we determine that p38α-SUMOylation functions as an authentic sensor and accelerator of reactive oxygen species generation via interaction with and activation of MK2 in the nucleus, and the ROS accumulation, in turn, promotes the SUMOylation of p38α by stabilizing the PIASxα protein. This precise regulatory mechanism is exploited by gastric cancer cells to create an internal environment for survival and, ultimately, metastasis. This study reveals novel insights into p38α-SUMOylation and its association with the intracellular oxidative stress response, which is closely related to the processes of gastric cancer. Furthermore, the PIASxα/p38α-SUMOylation/MK2 cis-axis may serve as a desirable therapeutic target in gastric cancer as targeting PIASxα, MK2, or a specific peptide region of p38α may reconcile the aberrant oxidative stress response in gastric cancer cells.

scholarly journals Dose-Dependent Effects of Cold Atmospheric Argon Plasma on the Mesenchymal Stem and Osteosarcoma Cells In Vitro

2021 ◽  
Vol 22 (13) ◽  
pp. 6797
Author(s):  
Artem M. Ermakov ◽  
Olga N. Ermakova ◽  
Vera A. Afanasyeva ◽  
Anton L. Popov
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cell Cycle ◽  
Stem Cells ◽  
Cancer Cells ◽  
Transcriptional Activity ◽  
Argon Plasma ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Normal Cells

The antimicrobial, anti-inflammatory and tissue-stimulating effects of cold argon atmospheric plasma (CAAP) accelerate its use in various fields of medicine. Here, we investigated the effects of CAAP at different radiation doses on mesenchymal stem cells (MSCs) and human osteosarcoma (MNNG/HOS) cells. We observed an increase in the growth rate of MSCs at sufficiently low irradiation doses (10–15 min) of CAAP, while the growth of MNNG/HOS cells was slowed down to 41% at the same irradiation doses. Using flow cytometry, we found that these effects are associated with cell cycle arrest and extended death of cancer cells by necrosis. Reactive oxygen species (ROS) formation was detected in both types of cells after 15 min of CAAP treatment. Evaluation of the genes’ transcriptional activity showed that exposure to low doses of CAAP activates the expression of genes responsible for proliferation, DNA replication, and transition between phases of the cell cycle in MSCs. There was a decrease in the transcriptional activity of most of the studied genes in MNNG/HOS osteosarcoma cancer cells. However, increased transcription of osteogenic differentiation genes was observed in normal and cancer cells. The selective effects of low and high doses of CAAP treatment on cancer and normal cells that we found can be considered in terms of hormesis. The low dose of cold argon plasma irradiation stimulated the vital processes in stem cells due to the slight generation of reactive oxygen species. In cancer cells, the same doses evidently lead to the formation of oxidative stress, which was accompanied by a proliferation inhibition and cell death. The differences in the cancer and normal cells’ responses are probably due to different sensitivity to exogenous oxidative stress. Such a selective effect of CAAP action can be used in the combined therapy of oncological diseases such as skin neoplasms, or for the removal of remaining cancer cells after surgical removal of a tumor.

Oridonin induces oxidative stress-mediated cancer cells apoptosis via targeting thioredoxin reductase

2021 ◽  
Vol 23 ◽  
Author(s):  
Dongzhu Duan ◽  
Xiaolu Feng ◽  
Dabo Pan ◽  
Le Wang ◽  
Yanru Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Malignant Tumors ◽  
Thioredoxin Reductase ◽  
Reactive Oxygen ◽  
Annexin V ◽  
Oxygen Species ◽  
Reduction Assay

Background: Thioredoxin reductase (TrxR) plays vital role in regulating cellular redox balance as well as redox-mediated signal transduction. Accumulating evidence supports that overactivation of TrxR is closely related to tumorigenesis and that targeting TrxR ablation reverses the growth of numerous malignant tumors, making TrxR a promising target for cancer chemotherapy. Thus, the discovery and development of molecules as promising anticancer agents that target TrxR is of great significance. Oridonin was shown to inhibit TrxR activity, but the detailed cellular mechanism is largely unknown. Objective: The study investigated the mechanism of action and underlying inhibitory properties of oridonin on TrxR in HeLa cells. Methods: A covalent docking was performed to reveal the possible interaction between oridonin and TrxR by Schrödinger Software Suite. TrxR activity was determined by 5,5’-dithiobis-2-nitrobenzoic acid reduction assay and endpoint insulin reduction assay. Sulforhodamine B and colony formation assay were employed to assess the viability and growth of cells. Reactive oxygen species level was measured by probe 2’, 7’-dichlorfluorescein diacetate, and dihydroethidium. Hoechst 33342 staining, caspase 3 activation, and fluorescein-5-isothiocyanate-conjugated Annexin V and propidium iodide double staining were used to evaluate apoptosis. Results: Here, we reported the oridonin as a potent inhibitor of TrxR. Inhibition of TrxR results in a decrease of thiols content and total glutathione elevates reactive oxygen species levels, and finally promotes oxidative stress-mediated apoptosis of cancer cells. Conclusion : Targeting TrxR by oridonin discloses a novel molecular mechanism underlying the biological action of oridonin and sheds light on developing oridonin as a potential tumor therapeutic agent.

Clinical aspects of reactive oxygen and nitrogen species

2004 ◽  
Vol 71 ◽  
pp. 121-133 ◽  
Author(s):  
Ascan Warnholtz ◽  
Maria Wendt ◽  
Michael August ◽  
Thomas Münzel
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Risk Factor ◽  
Endothelial Dysfunction ◽  
Vascular Tissue ◽  
Rapid Development ◽  
Reactive Oxygen ◽  
Clinical Aspects ◽  
No Production ◽  
Oxygen Species

Endothelial dysfunction in the setting of cardiovascular risk factors, such as hypercholesterolaemia, hypertension, diabetes mellitus and chronic smoking, as well as in the setting of heart failure, has been shown to be at least partly dependent on the production of reactive oxygen species in endothelial and/or smooth muscle cells and the adventitia, and the subsequent decrease in vascular bioavailability of NO. Superoxide-producing enzymes involved in increased oxidative stress within vascular tissue include NAD(P)H-oxidase, xanthine oxidase and endothelial nitric oxide synthase in an uncoupled state. Recent studies indicate that endothelial dysfunction of peripheral and coronary resistance and conductance vessels represents a strong and independent risk factor for future cardiovascular events. Ways to reduce endothelial dysfunction include risk-factor modification and treatment with substances that have been shown to reduce oxidative stress and, simultaneously, to stimulate endothelial NO production, such as inhibitors of angiotensin-converting enzyme or the statins. In contrast, in conditions where increased production of reactive oxygen species, such as superoxide, in vascular tissue is established, treatment with NO, e.g. via administration of nitroglycerin, results in a rapid development of endothelial dysfunction, which may worsen the prognosis in patients with established coronary artery disease.

Danshensu Rescues Ischemia/Reperfusion Caused Human Hepatocyte Death

2018 ◽  
Vol 17 (2) ◽  
pp. 117-121
Author(s):  
Sun Maw-Sheng ◽  
Liang Chun-Ya ◽  
Hsieh Po-Chun ◽  
Kuo Chan-Yen
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Caspase 3 ◽  
Ischemia Reperfusion ◽  
Oxygen Species ◽  
Good Strategy ◽  
Ros Accumulation ◽  
Dichlorofluorescin Diacetate ◽  
Hepatocyte Damage ◽  
Hepatocyte Death

Apoptosis of hepatocyte, under ischemia/reperfusion (IR) conditions, has been identified as an essential process in the progression of liver transplantation. Under these conditions, mitochondria can become a threat to the cell because of their capacity to generate reactive oxygen species (ROS). Additionally, ROS overproduction may induce inflammation. As ROS accumulation appears to cause hepatocyte damage or death, there has been considerable interest in identifying the candidate natural products involved and in developing strategies to reduce oxidative stress. In this study, we use Danshensu as a candidate product to speculate whether has the protective effect on apoptotic hepatocyte upon IR. To speculate the apoptotic phenomena was reversed by Danshensu, we detected the p53, cleaved-caspase 3 expression by western blotting, as well as caspase-3 activity. Additionally, we analyzed the ROS levels by 2′,7′-dichlorofluorescin diacetate (DCF-DA) staining. We also detected the cell viability by WST-1. Results showed that Danshensu alleviated hypoxia-caused cell apoptosis via ROS overproduction. We suggested that Danshensu is a good strategy for treating hepatocyte damage upon IR.

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