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Journal ArticleDOI

Reduction-oxidation pathways involved in cancer development: a systematic review of literature reviews.

16 Apr 2017-Oncotarget (Impact Journals)-Vol. 8, Iss: 31, pp 51888-51906
TL;DR: A global overview of the redox signaling pathways, which play a role in cancer formation, is provided and cancer prevention and treatment opportunities, which address redox pathways, are discussed.
Abstract: // Xīn Gao 1,2 and Ben Schottker 1,2,3 1 Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany 2 Network Aging Research, University of Heidelberg, Heidelberg, Germany 3 Institute of Health Care and Social Sciences, FOM University, Essen, Germany Correspondence to: Ben Schottker, email: // Keywords : neoplasm; oxidative stress; redox signaling; signal transduction; reactive oxygen species Received : November 04, 2016 Accepted : April 03, 2017 Published : April 16, 2017 Abstract Oxidative stress results from an imbalance of the reactive oxygen species/reactive nitrogen species (ROS/RNS) production and the oxidants defense system. Extensive research during the last decades has revealed that oxidative stress can mediate cancer initiation and development by leading not only to molecular damage but also to a disruption of reduction–oxidation (redox) signaling. In order to provide a global overview of the redox signaling pathways, which play a role in cancer formation, we conducted a systematic literature search in PubMed and ISI Web of Science and identified 185 relevant reviews published in the last 10 years. The 20 most frequently described pathways were selected to be presented in this systematic review and could be categorized into 3 groups: Intracellular ROS/RNS generating organelles and enzymes, signal transduction cascades kinases/phosphatases and transcription factors. Intracellular ROS/RNS generation organelles are mitochondria, endoplasmic reticulum and peroxisomes. Enzymes, including NOX, COX, LOX and NOS, are the most prominent enzymes generating ROS/RNS. ROS/RNS act as redox messengers of transmembrane receptors and trigger the activation or inhibition of signal transduction kinases/phosphatases, such as the family members of protein tyrosine kinases and protein tyrosine phosphatases. Furthermore, these reactions activate downstream signaling pathways including protein kinase of the MAPK cascade, PI3K and PKC. The kinases and phosphatases regulate the phosphorylation status of transcription factors including APE1/Ref-1, HIF-1α, AP-1, Nrf2, NF-κB, p53, FOXO, STAT, and β-catenin. Finally, we briefly discuss cancer prevention and treatment opportunities, which address redox pathways and further research needs.

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Citations
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01 Apr 2012
TL;DR: International experts in cancer prevention analyse global research on diet nutrition physical activity cancer and make public health policy recommendations, the fractions of cancer attributable to potentially modifiable factors are analyzed.
Abstract: physical activity and cancer fact sheet national cancer on this page what is physical activity what is known about the relationship between physical activity and cancer risk how might physical activity be, diet and cancer report american institute for cancer the american institute for cancer research aicr is the cancer charity that fosters research on diet and cancer prevention and educates the public about the results, download resources and toolkits world cancer research downloads for scientists from the wcrf aicr third expert report diet nutrition physical activity and cancer a global perspective, nutritional science university of washington school of public health school of public health nutritional science detailed course offerings time schedule are available for spring quarter 2019, 2019 aicr research conference american institute for about aicr we fund cutting edge research and give people practical tools and information to help them prevent and survive cancer more about aicr, agence fruits et l gumes frais aprifel the global fruit and veg newsletter is a monthly newsletter distributing to 29 countries involved in the promotion of the consumption of fruit and vegetable worldwide, world cancer research fund international we are experts in cancer prevention we analyse global research on diet nutrition physical activity cancer and make public health policy recommendations, the fractions of cancer attributable sciencedirect com a proportion of cancers at many body sites are attributable to potentially modifiable factors no global summaries of the preventable cancer burden have been, who controlling the global obesity epidemic more information obesity and overweight fact sheet who global strategy on diet physical activity and health who global database on body mass index, espen guidelines on nutrition in cancer patients gl nutrition in cancer patients outline o methods o1 basic information o2 methods o3 post publication impact a background a1 catabolic alterations in, un news global perspective human stories un news produces daily news content in arabic chinese english french kiswahili portuguese russian and spanish and weekly programmes in hindi urdu and bangla, recommended community strategies and measurements to table continued summary of recommended community strategies and measurements to prevent obesity in the united states strategies to encourage physical, food as medicine preventing treating the most dreaded food as medicine preventing treating the most dreaded diseases with diet, video resources bc cancer these videos help patients learn about their cancer and its treatment, prostate cancer nutrition and dietary supplements pdq nutrition methods and dietary supplements have been studied for prostate cancer prevention or treatment read about the history of research laboratory, who europe food safety food safety ingestion and handling of contaminated food causes significant illness and death worldwide across the who european region foodborne diseases, creating healthy food and eating environments policy and food and eating environments likely contribute to the increasing epidemic of obesity and chronic diseases over and above individual factors such as knowledge skills, health risks obesity prevention source harvard t h obesity and reproduction obesity can influence various aspects of reproduction from sexual activity to conception among women the association between, top nutrition schools undergraduate degree programs ncr want to know the top nutrition schools and best undergraduate degree programs here we review analyze rank rate them figure out which is best for you , overeating caloric restriction and breast cancer risk by this study analyzes the association of excessive energy intake and caloric restriction with breast cancer bc risk taking into account the individual, calcium what s best for your bones and health the possible increased risk of ovarian cancer high levels of galactose a sugar released by the digestion of lactose in milk have been studied as being, cancer protocol nutrition supplements cancer protocol nutrition supplements herbs enzymes note do not email me unless you would like a personalized protocol free with a suggested donation of 250

2,202 citations

Journal ArticleDOI
TL;DR: The critical and targetable redox-regulating enzymes, including mitochondrial electron transport chain complexes, NADPH oxidases (NOXs), enzymes related to glutathione metabolism, glutamate/cystine antiporter xCT, thioredoxin reductases (TrxRs), nuclear factor erythroid 2-related factor 2 (Nrf2), and their roles in regulating cellular ROS levels, drug resistance as well as their clinical significance are discussed.

361 citations

Journal ArticleDOI
TL;DR: The latest findings on the intricate relationship between mitochondrial dynamics and ROS production are reviewed, focusing mainly on its role in malignant disease.
Abstract: Mitochondria are organelles with a highly dynamic ultrastructure maintained by a delicate equilibrium between its fission and fusion rates. Understanding the factors influencing this balance is important as perturbations to mitochondrial dynamics can result in pathological states. As a terminal site of nutrient oxidation for the cell, mitochondrial powerhouses harness energy in the form of ATP in a process driven by the electron transport chain. Contemporaneously, electrons translocated within the electron transport chain undergo spontaneous side reactions with oxygen, giving rise to superoxide and a variety of other downstream reactive oxygen species (ROS). Mitochondrially-derived ROS can mediate redox signaling or, in excess, cause cell injury and even cell death. Recent evidence suggests that mitochondrial ultrastructure is tightly coupled to ROS generation depending on the physiological status of the cell. Yet, the mechanism by which changes in mitochondrial shape modulate mitochondrial function and redox homeostasis is less clear. Aberrant mitochondrial morphology may lead to enhanced ROS formation, which, in turn, may deteriorate mitochondrial health and further exacerbate oxidative stress in a self-perpetuating vicious cycle. Here, we review the latest findings on the intricate relationship between mitochondrial dynamics and ROS production, focusing mainly on its role in malignant disease.

323 citations

Journal ArticleDOI
TL;DR: Three natural antioxidants, which are quercetin, resveratrol and curcumin, will be focused mainly on, as well as their benefits on physical activity and on aging, which is expected to increase through the years and can get favorable benefits from a constant exercise activity.
Abstract: Physical exercise is considered to be one of the beneficial factors of a proper lifestyle and is nowadays seen as an indispensable element for good health, able to lower the risk of disorders of the cardiovascular, endocrine and osteomuscular apparatus, immune system diseases and the onset of potential neoplasms. A moderate and programmed physical exercise has often been reported to be therapeutic both in the adulthood and in aging, since capable to promote fitness. Regular exercise alleviates the negative effects caused by free radicals and offers many health benefits, including reduced risk of all-cause mortality, sarcopenia in the skeletal muscle, chronic disease, and premature death in elderly people. However, physical performance is also known to induce oxidative stress, inflammation, and muscle fatigue. Many efforts have been carried out to identify micronutrients and natural compounds, also known as nutraceuticals, able to prevent or attenuate the exercise-induced oxidative stress and inflammation. The aim of this review is to discuss the benefits deriving from a constant physical activity and by the intake of antioxidant compounds to protect the body from oxidative stress. The attention will be focused mainly on three natural antioxidants, which are quercetin, resveratrol and curcumin. Their properties and activity will be described, as well as their benefits on physical activity and on aging, which is expected to increase through the years and can get favorable benefits from a constant exercise activity.

292 citations


Cites background from "Reduction-oxidation pathways involv..."

  • ...Mitochondria are also particularly vulnerable to oxidative damage and are central to the theory of aging [20, 21]....

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Journal ArticleDOI
30 Jul 2019-Cells
TL;DR: The importance of reactive oxygen species (ROS) in regulating cell functioning and communication among themselves and the relevance of ROS in therapy concepts is addressed here.
Abstract: The importance of reactive oxygen species (ROS) has been gradually acknowledged over the last four decades. Initially perceived as unwanted products of detrimental oxidative stress, they have been upgraded since, and now ROS are also known to be essential for the regulation of physiological cellular functions through redox signaling. In the majority of cases, metabolic demands, along with other stimuli, are vital for ROS formation and their actions. In this review, we focus on the role of ROS in regulating cell functioning and communication among themselves. The relevance of ROS in therapy concepts is also addressed here.

174 citations

References
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Journal ArticleDOI
TL;DR: Attention is focussed on the ROS/RNS-linked pathogenesis of cancer, cardiovascular disease, atherosclerosis, hypertension, ischemia/reperfusion injury, diabetes mellitus, neurodegenerative diseases, rheumatoid arthritis, and ageing.

12,240 citations


"Reduction-oxidation pathways involv..." refers background in this paper

  • ...Therefore, ROS/RNS, especially hydrogen peroxide (H2O2) and nitric oxide (NO), can act as second messengers by activating or inhibiting protein functions [2-4]....

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  • ...For instance, ROS play a part in antioxidant defense systems to maintain redox homeostasis even though they are strong oxidants themselves [3]....

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  • ...Excessive levels of ROS/RNS are able to react with proteins, lipids and nucleic acids, and may exert negative effects on these molecules [3, 7]....

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Journal ArticleDOI
TL;DR: Some key aspects of Wnt/beta-catenin signaling in human diseases including congenital malformations, cancer, and osteoporosis are highlighted, and potential therapeutic implications are discussed.

4,926 citations


"Reduction-oxidation pathways involv..." refers background in this paper

  • ...hepatocellular cancer [73]), which benefits cancer growth [71-73]....

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  • ...Under unstimulated condition, β-catenin is inactivated by forming a destruction complex with axin, adenomatous polyposis coli, glycogen synthase kinase 3 and casein kinase 1 [71, 72]....

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  • ...Wnt can activate β-catenin transcriptional activity by binding to a Frizzled receptor and low-density lipoprotein receptor-related protein 5 and 6 [71, 72]....

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  • ...The Wnt/β-catenin signaling pathway is implicated in cell proliferation, cell adhesion and cell fate decision [58, 71, 73]....

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Journal ArticleDOI
TL;DR: Observations to date suggest that oxidative stress, chronic inflammation, and cancer are closely linked.

3,922 citations


"Reduction-oxidation pathways involv..." refers background in this paper

  • ...Oxidative stress induced disruption of signaling pathways may promote cancer cell survival, proliferation, invasion, angiogenesis, inhibition of apoptosis and chemo- and radio- therapy resistance [9, 11]....

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  • ...Besides molecular damage, increased ROS/ RNS levels are involved in disruption of redox signaling and regulation [9]....

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Journal ArticleDOI
TL;DR: Signal transducer and activator of transcription proteins are central in determining whether immune responses in the tumour microenvironment promote or inhibit cancer, and STAT3 is a promising target to redirect inflammation for cancer therapy.
Abstract: Commensurate with their roles in regulating cytokine-dependent inflammation and immunity, signal transducer and activator of transcription (STAT) proteins are central in determining whether immune responses in the tumour microenvironment promote or inhibit cancer. Persistently activated STAT3 and, to some extent, STAT5 increase tumour cell proliferation, survival and invasion while suppressing anti-tumour immunity. The persistent activation of STAT3 also mediates tumour-promoting inflammation. STAT3 has this dual role in tumour inflammation and immunity by promoting pro-oncogenic inflammatory pathways, including nuclear factor-kappaB (NF-kappaB) and interleukin-6 (IL-6)-GP130-Janus kinase (JAK) pathways, and by opposing STAT1- and NF-kappaB-mediated T helper 1 anti-tumour immune responses. Consequently, STAT3 is a promising target to redirect inflammation for cancer therapy.

3,564 citations


"Reduction-oxidation pathways involv..." refers background in this paper

  • ...STAT proteins are induced by activation of cytokine-Janus kinase (JAK) signaling [69, 70]....

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  • ...STAT proteins control inflammatory responses and are involved in cancer development [70]....

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  • ...STAT3 and STAT5 are upregulated in numerous types of cancer cells and promote cancer growth, angiogenesis and metastasis [70]....

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  • ...In particular, activation of STAT3 leads to expression of interleukin-6 and COX-2 which mediate cancerpromoting immunity [70]....

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  • ...Seven STAT proteins have been identified in mammals: STAT1-4, STAT5A, STAT5B and STAT6 [69, 70]....

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Journal ArticleDOI
14 May 2007-Oncogene
TL;DR: Recent findings and hypotheses on the role of MAPK pathways in cancer are discussed, with a focus on stress-activated pathways, which largely seem to counteract malignant transformation.
Abstract: Cancer can be perceived as a disease of communication between and within cells. The aberrations are pleiotropic, but mitogen-activated protein kinase (MAPK) pathways feature prominently. Here, we discuss recent findings and hypotheses on the role of MAPK pathways in cancer. Cancerous mutations in MAPK pathways are frequently mostly affecting Ras and B-Raf in the extracellular signal-regulated kinase pathway. Stress-activated pathways, such as Jun N-terminal kinase and p38, largely seem to counteract malignant transformation. The balance and integration between these signals may widely vary in different tumours, but are important for the outcome and the sensitivity to drug therapy.

2,605 citations


"Reduction-oxidation pathways involv..." refers background in this paper

  • ...The activated p38 MAPK targets multiple transcription factors, such as p38, MEF2 and ATF-2 [34]....

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  • ...Then the MAPKKK activate MAP2K4/7 which subsequently activates JNKs. Oncotarget51896www.impactjournals.com/oncotarget Similar to p38 MAPK, the activated JNKs are able to phosphorylate several transcription factors, like c-Jun, ATF-2 and STAT3 [29]....

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  • ...Therefore, the ERK1/2 pathway can promote cancer development by maintaining cancer cell survival and stimulating cancer cell proliferation and metastasis [30, 34]....

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  • ...11 Mitogen-activated protein kinase 41 6 [29-34]...

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  • ...In addition, mutations in genes which encode for RAS and RAF are involved in cancer development [34]....

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