scholarly journals Implications of Oxidative Stress in Glioblastoma Multiforme Following Treatment with Purine Derivatives

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 950
Author(s):  
Marta Orlicka-Płocka ◽  
Agnieszka Fedoruk-Wyszomirska ◽  
Dorota Gurda-Woźna ◽  
Paweł Pawelczak ◽  
Patrycja Krawczyk ◽  
...  

Recently, small compound-based therapies have provided new insights into the treatment of glioblastoma multiforme (GBM) by inducing oxidative impairment. Kinetin riboside (KR) and newly designed derivatives (8-azaKR, 7-deazaKR) selectively affect the molecular pathways crucial for cell growth by interfering with the redox status of cancer cells. Thus, these compounds might serve as potential alternatives in the oxidative therapy of GBM. The increased basal levels of reactive oxygen species (ROS) in GBM support the survival of cancer cells and cause drug resistance. The simplest approach to induce cell death is to achieve the redox threshold and circumvent the antioxidant defense mechanisms. Consequently, cells become more sensitive to oxidative stress (OS) caused by exogenous agents. Here, we investigated the effect of KR and its derivatives on the redox status of T98G cells in 2D and 3D cell culture. The use of spheroids of T98G cells enabled the selection of one derivative—7-deazaKR—with comparable antitumor activity to KR. Both compounds induced ROS generation and genotoxic OS, resulting in lipid peroxidation and leading to apoptosis. Taken together, these results demonstrated that KR and 7-deazaKR modulate the cellular redox environment of T98G cells, and vulnerability of these cells is dependent on their antioxidant capacity.

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Jiahui Liu ◽  
Zhichong Wang

Reactive oxygen species (ROS) are closely related to tumorgenesis. Under hypoxic environment, increased levels of ROS induce the expression of hypoxia inducible factors (HIFs) in cancer stem cells (CSCs), resulting in the promotion of the upregulation of CSC markers, and the reduction of intracellular ROS level, thus facilitating CSCs survival and proliferation. Although the ROS level is regulated by powerful antioxidant defense mechanisms in cancer cells, it is observed to remain higher than that in normal cells. Cancer cells may be more sensitive than normal cells to the accumulation of ROS; consequently, it is supposed that increased oxidative stress by exogenous ROS generation therapy has an effect on selectively killing cancer cells without affecting normal cells. This paper reviews the mechanisms of redox regulation in CSCs and the pivotal role of ROS in anticancer treatment.


Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 4001
Author(s):  
Dominika Zajac

Asthma represents one of the most common medical issues in the modern world. It is a chronic inflammatory disease characterized by persistent inflammation of the airways and disturbances in redox status, leading to hyperresponsiveness of bronchi and airway obstruction. Apart from classical risk factors such as air pollution, family history, allergies, or obesity, disturbances of the levels of micronutrients lead to impairments in the defense mechanisms of the affected organism against oxidative stress and proinflammatory stimuli. In the present review, the impact of micronutrients on the prevalence, severity, and possible risk factors of asthma is discussed. Although the influence of classical micronutrients such as selenium, copper, or zinc are well known, the effects of those such as iodine or manganese are only rarely mentioned. As a consequence, the aim of this paper is to demonstrate how disturbances in the levels of micronutrients and their supplementation might affect the course of asthma.


2018 ◽  
Vol 6 (25) ◽  
pp. 4223-4231 ◽  
Author(s):  
Jiacheng Zhao ◽  
Hongxu Lu ◽  
Yin Yao ◽  
Sylvia Ganda ◽  
Martina H. Stenzel

Internalization of rod-like micelles by breast cancer cells is significantly affected by the stiffness of nano-rods.


2014 ◽  
Vol 5 (8) ◽  
pp. 1909-1914 ◽  
Author(s):  
Lijuan Sun ◽  
Cheng Luo ◽  
Jiankang Liu

Cancer cells are usually under higher levels of oxidative stress compared to normal cells.


Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1838
Author(s):  
Feroza K. Choudhury

Mitochondrial redox metabolism is the central component in the cellular metabolic landscape, where anabolic and catabolic pathways are reprogrammed to maintain optimum redox homeostasis. During different stages of cancer, the mitochondrial redox status plays an active role in navigating cancer cells’ progression and regulating metabolic adaptation according to the constraints of each stage. Mitochondrial reactive oxygen species (ROS) accumulation induces malignant transformation. Once vigorous cell proliferation renders the core of the solid tumor hypoxic, the mitochondrial electron transport chain mediates ROS signaling for bringing about cellular adaptation to hypoxia. Highly aggressive cells are selected in this process, which are capable of progressing through the enhanced oxidative stress encountered during different stages of metastasis for distant colonization. Mitochondrial oxidative metabolism is suppressed to lower ROS generation, and the overall cellular metabolism is reprogrammed to maintain the optimum NADPH level in the mitochondria required for redox homeostasis. After reaching the distant organ, the intrinsic metabolic limitations of that organ dictate the success of colonization and flexibility of the mitochondrial metabolism of cancer cells plays a pivotal role in their adaptation to the new environment.


2020 ◽  
Vol 9 (3) ◽  
pp. 191-199 ◽  
Author(s):  
Fatemeh Jamshidi-kia ◽  
Joko Priyanto Wibowo ◽  
Mostafa Elachouri ◽  
Rohollah Masumi ◽  
Alizamen Salehifard-Jouneghani ◽  
...  

Free radicals are constructed by natural physiological activities in the human cells as well as in the environment. They may be produced as a result of diet, smoking, exercise, inflammation, exposure to sunlight, air pollutants, stress, alcohol and drugs. Imbalanced redox status may lead to cellular oxidative stress, which can damage the cells of the body, resulting in an incidence of various diseases. If the endogenous antioxidants do not stop the production of reactive metabolites, they will be needed to bring about a balance in redox status. Natural antioxidants, for example plants, play an important part in this context. This paper seeks to report the available evidence about oxidative stress and the application of plants as antioxidant agents to fight free radicals in the human body. For this purpose, to better understand oxidative stress, the principles of free radical production, the role of free radicals in diseases, antioxidant defense mechanisms, and the role of herbs and diet in oxidative stress are discussed.


2011 ◽  
Vol 300 (6) ◽  
pp. E1047-E1058 ◽  
Author(s):  
Christine Ruggiero ◽  
Marilyn Ehrenshaft ◽  
Ellen Cleland ◽  
Krisztian Stadler

Obesity and metabolic syndrome are associated with an increased risk for several diabetic complications, including diabetic nephropathy and chronic kidney diseases. Oxidative stress and mitochondrial dysfunction are often proposed mechanisms in various organs in obesity models, but limited data are available on the kidney. Here, we fed a lard-based high-fat diet to mice to investigate structural changes, cellular and subcellular oxidative stress and redox status, and mitochondrial biogenesis and function in the kidney. The diet induced characteristic changes, including glomerular hypertrophy, fibrosis, and interstitial scarring, which were accompanied by a proinflammatory transition. We demonstrate evidence for oxidative stress in the kidney through 3-nitrotyrosine and protein radical formation on high-fat diet with a contribution from iNOS and NOX-4 as well as increased generation of mitochondrial oxidants on carbohydrate- and lipid-based substrates. The increased H2O2 emission in the mitochondria suggests altered redox balance and mitochondrial ROS generation, contributing to the overall oxidative stress. No major derailments were observed in respiratory function or biogenesis, indicating preserved and initially improved bioenergetic parameters and energy production. We suggest that, regardless of the oxidative stress events, the kidney developed an adaptation to maintain normal respiratory function as a possible response to an increased lipid overload. These findings provide new insights into the complex role of oxidative stress and mitochondrial redox status in the pathogenesis of the kidney in obesity and indicate that early oxidative stress-related changes, but not mitochondrial bioenergetic dysfunction, may contribute to the pathogenesis and development of obesity-linked chronic kidney diseases.


2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Shy Cian Khor ◽  
Wan Zurinah Wan Ngah ◽  
Yasmin Anum Mohd Yusof ◽  
Norwahidah Abdul Karim ◽  
Suzana Makpol

During aging, oxidative stress affects the normal function of satellite cells, with consequent regeneration defects that lead to sarcopenia. This study aimed to evaluate tocotrienol-rich fraction (TRF) modulation in reestablishing the oxidative status of myoblasts during replicative senescence and to compare the effects of TRF with other antioxidants (α-tocopherol (ATF) andN-acetyl-cysteine (NAC)). Primary human myoblasts were cultured to young, presenescent, and senescent phases. The cells were treated with antioxidants for 24 h, followed by the assessment of free radical generation, lipid peroxidation, antioxidant enzyme mRNA expression and activities, and the ratio of reduced to oxidized glutathione. Our data showed that replicative senescence increased reactive oxygen species (ROS) generation and lipid peroxidation in myoblasts. Treatment with TRF significantly diminished ROS production and decreased lipid peroxidation in senescent myoblasts. Moreover, the gene expression of superoxide dismutase(SOD2), catalase(CAT),and glutathione peroxidase(GPX1)was modulated by TRF treatment, with increased activity of superoxide dismutase and catalase and reduced glutathione peroxidase in senescent myoblasts. In comparison to ATF and NAC, TRF was more efficient in heightening the antioxidant capacity and reducing free radical insults. These results suggested that TRF is able to ameliorate antioxidant defense mechanisms and improves replicative senescence-associated oxidative stress in myoblasts.


Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 510
Author(s):  
Giuseppina Barrera ◽  
Marie Angele Cucci ◽  
Margherita Grattarola ◽  
Chiara Dianzani ◽  
Giuliana Muzio ◽  
...  

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.


Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4458
Author(s):  
Quentin Lion ◽  
Andre Pichette ◽  
Mouadh Mihoub ◽  
Vakhtang Mshvildadze ◽  
Jean Legault

UV-B and IR-A radiation are important inducers of biological changes in skin involving ROS generation. The overloading of antioxidant defense mechanisms by ROS production could lead to photoaging and photocarcinogenesis processes. Various traditional usages are reported for Aralia nudicaulis L. extracts, including treatment of dermatological disorders. Antioxidant and anti-inflammatory properties have already been reported for other Aralia species possibly due to the presence of phenolic compounds. However, the phenolic composition and the potential activity of A. nudicaulis rhizomes extract against oxidative stress and UV/IR damages have not been investigated. The main aims of this study were to prepare a fraction enriched in phenolic compounds (FEPC) from A. nudicaulis rhizomes, to identify its major phenolic compounds and to assess its potential for protective effects against oxidative stress induced by UV-B, IR-A or inflammation. A quantitative LC-MS study of FEPC shows that chlorogenic, caffeic and protocatechuic acids are the main phenolic compounds present, with concentrations of 15.6%, 15.3% and 4.8% of the total composition, respectively. With a validated analytical method, those compounds were quantified over different stages of the growing period. As for biological potential, first this extract demonstrates antioxidant and anti-inflammatory activities. Furthermore, ROS generation induced by IR-A and UV-B were strongly inhibited by A. nudicaulis extract, suggesting that Aralia nudicaulis L. rhizome extract could protect dermal cells against oxidative stress induced by UV-B and IR-A.


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