scholarly journals Metabolic Potential of Cancer Cells in Context of the Metastatic Cascade

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2035
Author(s):  
Mohaned Benzarti ◽  
Catherine Delbrouck ◽  
Laura Neises ◽  
Nicole Kiweler ◽  
Johannes Meiser
Keyword(s):  
Cancer Cells ◽  
Primary Tumour ◽  
Redox Homeostasis ◽  
Redox Balance ◽  
Cellular Heterogeneity ◽  
Metastatic Progression ◽  
Metabolic Potential ◽  
Metastatic Cascade ◽  
One Carbon Metabolism ◽  
Primary Tumour Growth

The metastatic cascade is a highly plastic and dynamic process dominated by cellular heterogeneity and varying metabolic requirements. During this cascade, the three major metabolic pillars, namely biosynthesis, RedOx balance, and bioenergetics, have variable importance. Biosynthesis has superior significance during the proliferation-dominated steps of primary tumour growth and secondary macrometastasis formation and only minor relevance during the growth-independent processes of invasion and dissemination. Consequently, RedOx homeostasis and bioenergetics emerge as conceivable metabolic key determinants in cancer cells that disseminate from the primary tumour. Within this review, we summarise our current understanding on how cancer cells adjust their metabolism in the context of different microenvironments along the metastatic cascade. With the example of one-carbon metabolism, we establish a conceptual view on how the same metabolic pathway can be exploited in different ways depending on the current cellular needs during metastatic progression.

scholarly journals Role of Reductive versus Oxidative Stress in Tumor Progression and Anticancer Drug Resistance

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 758
Author(s):  
Kyung-Soo Chun ◽  
Do-Hee Kim ◽  
Young-Joon Surh
Keyword(s):  
Cancer Cells ◽  
Metabolic Pathways ◽  
Redox Homeostasis ◽  
Redox Balance ◽  
Therapy Resistance ◽  
Related Factor ◽  
Nuclear Factor ◽  
Cellular Redox ◽  
Reductive Stress

Redox homeostasis is not only essential for the maintenance of normal physiological functions, but also plays an important role in the growth, survival, and therapy resistance of cancer cells. Altered redox balance and consequent disruption of redox signaling are implicated in the proliferation and progression of cancer cells and their resistance to chemo- and radiotherapy. The nuclear factor erythroid 2 p45-related factor (Nrf2) is the principal stress-responsive transcription factor that plays a pivotal role in maintaining cellular redox homeostasis. Aberrant Nrf2 overactivation has been observed in many cancerous and transformed cells. Uncontrolled amplification of Nrf2-mediated antioxidant signaling results in reductive stress. Some metabolic pathways altered due to reductive stress have been identified as major contributors to tumorigenesis. This review highlights the multifaceted role of reductive stress in cancer development and progression.

scholarly journals Understanding of ROS-Inducing Strategy in Anticancer Therapy

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Su Ji Kim ◽  
Hyun Soo Kim ◽  
Young Rok Seo
Keyword(s):  
Oxidative Stress ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Molecular Mechanisms ◽  
Redox Homeostasis ◽  
Biological Response ◽  
Buthionine Sulfoximine ◽  
Redox Balance ◽  
Anticancer Therapy ◽  
Therapeutic Effects

Redox homeostasis is essential for the maintenance of diverse cellular processes. Cancer cells have higher levels of reactive oxygen species (ROS) than normal cells as a result of hypermetabolism, but the redox balance is maintained in cancer cells due to their marked antioxidant capacity. Recently, anticancer therapies that induce oxidative stress by increasing ROS and/or inhibiting antioxidant processes have received significant attention. The acceleration of accumulative ROS disrupts redox homeostasis and causes severe damage in cancer cells. In this review, we describe ROS-inducing cancer therapy and the anticancer mechanism employed by prooxidative agents. To understand the comprehensive biological response to certain prooxidative anticancer drugs such as 2-methoxyestradiol, buthionine sulfoximine, cisplatin, doxorubicin, imexon, and motexafin gadolinium, we propose and visualize the drug-gene, drug-cell process, and drug-disease interactions involved in oxidative stress induction and antioxidant process inhibition as well as specific side effects of these drugs using pathway analysis with a big data-based text-mining approach. Our review will be helpful to improve the therapeutic effects of anticancer drugs by providing information about biological changes that occur in response to prooxidants. For future directions, there is still a need for pharmacogenomic studies on prooxidative agents as well as the molecular mechanisms underlying the effects of the prooxidants and/or antioxidant-inhibitor agents for effective anticancer therapy through selective killing of cancer cells.

scholarly journals Oxidative Stress in the Tumor Microenvironment and Its Relevance to Cancer Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 986
Author(s):  
Nada S. Aboelella ◽  
Caitlin Brandle ◽  
Timothy Kim ◽  
Zhi-Chun Ding ◽  
Gang Zhou
Keyword(s):  
Oxidative Stress ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Redox Homeostasis ◽  
Tumor Rejection ◽  
Oxygen Species ◽  
Antitumor Effects ◽  
Key Drivers ◽  
Cancer Immunotherapies ◽  
The Impact

It has been well-established that cancer cells are under constant oxidative stress, as reflected by elevated basal level of reactive oxygen species (ROS), due to increased metabolism driven by aberrant cell growth. Cancer cells can adapt to maintain redox homeostasis through a variety of mechanisms. The prevalent perception about ROS is that they are one of the key drivers promoting tumor initiation, progression, metastasis, and drug resistance. Based on this notion, numerous antioxidants that aim to mitigate tumor oxidative stress have been tested for cancer prevention or treatment, although the effectiveness of this strategy has yet to be established. In recent years, it has been increasingly appreciated that ROS have a complex, multifaceted role in the tumor microenvironment (TME), and that tumor redox can be targeted to amplify oxidative stress inside the tumor to cause tumor destruction. Accumulating evidence indicates that cancer immunotherapies can alter tumor redox to intensify tumor oxidative stress, resulting in ROS-dependent tumor rejection. Herein we review the recent progresses regarding the impact of ROS on cancer cells and various immune cells in the TME, and discuss the emerging ROS-modulating strategies that can be used in combination with cancer immunotherapies to achieve enhanced antitumor effects.

Acrylamide-encapsulated glucose oxidase inhibits breast cancer cell viability

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Trëndelina Rrustemi ◽  
Öykü Gönül Geyik ◽  
Ali Burak Özkaya ◽  
Taylan Kurtuluş Öztürk ◽  
Zeynep Yüce ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Glucose Oxidase ◽  
Cancer Cells ◽  
Half Life ◽  
Neutralizing Antibodies ◽  
Redox Homeostasis ◽  
Proteinase K ◽  
Dependent Manner ◽  
Production Of Hydrogen ◽  
Mcf 7

AbstractObjectivesCancer cells modulate metabolic pathways to ensure continuity of energy, macromolecules and redox- homeostasis. Although these vulnerabilities are often targeted individually, targeting all with an enzyme may prove a novel approach. However, therapeutic enzymes are prone to proteolytic degradation and neutralizing antibodies leading to a reduced half-life and effectiveness. We hypothesized that glucose oxidase (GOX) enzyme that catalyzes oxidation of glucose and production of hydrogen peroxide, may hit all these targets by depleting glucose; crippling anabolic pathways and producing reactive oxygen species (ROS); unbalancing redox homeostasis.MethodsWe encapsulated GOX in an acrylamide layer and then performed activity assays in denaturizing settings to determine protection provided by encapsulation. Afterwards, we tested the effects of encapsulated (enGOX) and free (fGOX) enzyme on MCF-7 breast cancer cells.ResultsGOX preserved 70% of its activity following encapsulation. When fGOX and enGOX treated with guanidinium chloride, fGOX lost approximately 72% of its activity, while enGOX only lost 30%. Both forms demonstrated remarkable resilience against degradation by proteinase K and inhibited viability of MCF-7 cells in an activity-dependent manner.ConclusionsEncapsulation provided protection to GOX against denaturation without reducing its activity, which would prolong half-life of the enzyme when administered intravenously.

Extraction of ursolic acid from Ocimum sanctum and synthesis of its novel derivatives: effects on extracellular homocysteine, dihydrofolate reductase activity and proliferation of HepG2 human hepatoma cells

Pteridines ◽  
2013 ◽  
Vol 24 (3) ◽  
pp. 191-199 ◽  
Author(s):  
Apsara Batra ◽  
V. Girija Sastry
Keyword(s):  
Cancer Cells ◽  
Ursolic Acid ◽  
Dihydrofolate Reductase ◽  
Carbon Metabolism ◽  
Hepatoma Cells ◽  
Ocimum Sanctum ◽  
Human Hepatoma ◽  
Human Hepatoma Cells ◽  
Anti Cancer ◽  
One Carbon Metabolism

AbstractThe objective of the present study was to extract ursolic acid (UA) from Ocimum sanctum, to synthesize its bioactive derivatives, evaluate the anti-cancer effect of its derivatives and to establish the possible mechanism of action. In the present report, we extracted UA from whole plant of O. sanctum, synthesized its novel derivatives and investigated their effect on homocysteine metabolism and dihydrofolate reductase (DHFR) activity of HepG2 cells. UA and its derivatives UA-1, UA-2 and UA-3 down-regulated DHFR activity and increased extracellular homocysteine. UA-2 showed significant anti-proliferation activity in cancer cells. Cancer cells have increased the requirement of pyrimidine base thymidylate due to rapid cell division. Thymidylate biosynthesis depends on sufficient pools of folate dependent enzymes like DHFR. In the present study, we examined the UA and its derivatives mediated perturbation of DHFR activity and extracellular homocysteine in HepG2 human hepatoma cells. After incubation with UA-2, a potent inhibition of DHFR activity was observed. Our results showed that derivatization of UA might adversely affect DHFR activity. Measurement of extracellular homocysteine indicated impaired one-carbon metabolism in cells treated with UA derivatives. In conclusion, our data suggest an anti-cancer role of UA and its derivatives via inhibition of one-carbon metabolism.

scholarly journals NAC selectively inhibit cancer telomerase activity: A higher redox homeostasis threshold exists in cancer cells

Redox Biology ◽  
2016 ◽  
Vol 8 ◽  
pp. 91-97 ◽  
Author(s):  
Pengying Li ◽  
Meilin Wu ◽  
Jing Wang ◽  
Yilun Sui ◽  
Shanlin Liu ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Redox Homeostasis ◽  
Telomerase Activity

Effects of iron-related compounds and bilirubin on redox homeostasis in endometriosis and its malignant transformations

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Hiroshi Shigetomi ◽  
Shogo Imanaka ◽  
Hiroshi Kobayashi
Keyword(s):  
Oxidative Stress ◽  
Redox Homeostasis ◽  
Redox Balance ◽  
Heme Iron ◽  
Total Iron ◽  
University Hospital ◽  
Free Iron ◽  
Significant Difference ◽  
Iron Heme ◽  
Related Compounds

Abstract Objectives The balance between oxidative stress and antioxidant defense has been reported to differ between women with endometriosis and patients with its malignant transformation. The aim of this study is to investigate changes in redox balance in endometriosis and endometriosis-related ovarian cancer (EAOC) by simultaneously measuring iron-related compounds and bilirubin. Methods This study included 235 patients with a histopathologically confirmed diagnosis of endometriosis (n=178) and EAOC (n=57). Cyst fluid samples were collected in Nara Medical University hospital from January 2013 to May 2019. The levels of iron-related compounds (total iron, heme iron, free iron, oxyhemoglobin [oxyHb], methemoglobin [metHb], and metHb/oxyHb ratio) and bilirubin were measured. Results Total iron, heme iron, free iron, metHb/oxyHb ratio, and bilirubin were significantly elevated in endometriosis compared to EAOC. In both endometriosis and EAOC, iron-related compounds in the cyst were correlated with each other. There was no statistically significant difference in oxyHb and metHb levels between the two groups, but the metHb/oxyHb ratio was significantly higher in endometriosis than in EAOC. Bilirubin was positively correlated with total iron and free iron in EAOC, but there was no correlation between bilirubin and iron-related compounds in endometriosis. Conclusions Iron-induced oxidative stress in endometriosis may exceed bilirubin-dependent antioxidant capability, while redox homeostasis in EAOC can be maintained by at least bilirubin.

scholarly journals Redox Homeostasis and Metabolism in Cancer: A Complex Mechanism and Potential Targeted Therapeutics

2020 ◽  
Vol 21 (9) ◽  
pp. 3100 ◽  
Author(s):  
Alia Ghoneum ◽  
Ammar Yasser Abdulfattah ◽  
Bailey Olivia Warren ◽  
Junjun Shu ◽  
Neveen Said
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
Metabolic Pathways ◽  
Redox Homeostasis ◽  
Ros Production ◽  
Biological Processes ◽  
Survival Pathways ◽  
Oncogenic Mutations ◽  
And Oxidative Stress ◽  
Shed Light

Reactive Oxygen Species or “ROS” encompass several molecules derived from oxygen that can oxidize other molecules and subsequently transition rapidly between species. The key roles of ROS in biological processes are cell signaling, biosynthetic processes, and host defense. In cancer cells, increased ROS production and oxidative stress are instigated by carcinogens, oncogenic mutations, and importantly, metabolic reprograming of the rapidly proliferating cancer cells. Increased ROS production activates myriad downstream survival pathways that further cancer progression and metastasis. In this review, we highlight the relation between ROS, the metabolic programing of cancer, and stromal and immune cells with emphasis on and the transcription machinery involved in redox homeostasis, metabolic programing and malignant phenotype. We also shed light on the therapeutic targeting of metabolic pathways generating ROS as we investigate: Orlistat, Biguandes, AICAR, 2 Deoxyglucose, CPI-613, and Etomoxir.

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