Obesity, maternal malnutrition, or obesogenic maternal diet upon gestation, but not in the post-weaning period [ 42 ], is associated with augmented oxidative stress markers and diminished antioxidant capability in the offspring, resulting in diabetogenic effects [ 43 , 44 ]. Concurrently, antioxidant supplementation could significantly attenuate obesity in their offspring [ 45 ]. Nutrition may trigger epigenetic changes in perinatal development into adulthood via different pathways, such as metabolic risk factor progression and oxidative stress generation.
A previous study demonstrated that after glucose intake, mononuclear MNC and polymorphonuclear PMN leukocytes of normal subjects generate ROS and induce inflammation due to excess micronutrients [ 46 ]. Similarly, after lipid intake, leukocytes in normal subjects may also significantly induce ROS generation and inflammation; protein intake can trigger ROS generation, but to a much lesser degree than glucose and lipid intake can [ 47 ]. Postprandial oxidative stress might increase due to excessive caloric intake, which abnormally increases blood glucose, free fatty acids FFA , and triglycerides circulating in the blood.
Besides mitochondria, ROS production by leukocytes is also induced by the caloric amount, as previous studies indicated that caloric limit led to a decent reduction in ROS production via lipid peroxidation and protein carboxylation [ 51 , 52 , 53 ]. Inappropriate lifestyle patterns of an individual, including physical inactivity or obesity, can also cause ROS production in the postprandial state. As a result, obese individuals experience pernicious and acute oxidative stress after a fatty meal, compared to responses of the non-obese well-fitted individuals [ 54 ].
Inconsistent data exist regarding the outcome of exercise in postprandial oxidative stress. Although exercise is thought as a tool to increase endogenous antioxidant defenses, numerous researchers have been unsuccessful in showing a positive effect of physical activity on postprandial oxidative stress [ 55 , 56 , 57 ]. Cooking method can also have a postprandial impact on oxidative metabolism. Protein- and fat-rich food cooked quickly under high temperatures lead to the formation of dietary advanced glycation end products AGEs [ 58 ]. Studies showed that a single oral challenge by AGEs coke caused severe postprandial endothelial dysfunction, as illustrated by a significant reduction in flow-mediated dilatation both in diabetic and in healthy subjects [ 59 ].
Nutritive AGEs appear to affect reproductively challenged women as well. A study in women with polycystic ovarian syndrome PCOS showed that low-AGE meals in combination with six-month treatment with orlistat a lipase inhibitor led to a significant improvement of their hormonal profile and body mass index BMI [ 60 ].
Taken together, increasing evidence demonstrates that nutrition triggers major oxidative and inflammatory imbalances in the postprandial state. Indeed, postprandial hyperlipidemia and hyperglycemia, or so-called postprandial dysfunction in the body, are gradually gaining vital consideration as major risk factors for some diseases. Continuous accumulation of all these imbalances during the constant postprandial state that symbolizes current lifestyles may contribute to the pathophysiology of reproductive and metabolic disorders Figure 1.
Overnutrition and decreased physical activity lead to overloaded glucose and free fatty acid FFA levels in cells. Their conversion into energy is supplemented by augmented free radical generation oxidative stress. The muscle adipocytes can defend themselves from this situation and exhibit insulin resistance, aiming to decrease glucose and FFA permeation into the cells.
Inflammation, Oxidative Stress, and Cancer: Dietary Approaches for Cancer Prevention
This last condition is clinically characterized by increased postprandial hyperglycemia. Postprandial hyperglycemia induces oxidative stress. Moreover, the cluster of risk factors that accompany insulin resistance also contributes to CVD development. Red colored arrow represents overload Adapted from [ 49 ]. Nutrient consumption elicits a major oxidative and inflammatory effect at the cellular level, which alters tissue metabolism. These active but metabolically distressed tissues interacting with nutrients further augment oxidative stress, eventually resulting in an infinite vicious cycle Figure 2.
Nutrition mediates oxidative stress at the metabolic tissue level. Dietary fat lipids induces intracellular lipid accumulation in the liver and subsequently causes the inflammatory response and ER stress, which ultimately results in oxidative stress- and insulin resistance-induced liver dysfunction. A nutritious diet can induce the inflammatory response and impair FoxO1 expression, adipokine secretions, and antioxidant enzyme activity in the adipose tissue, resulting in an increased ROS generation, which ultimately causes dysfunction of the adipose tissue. Overfeeding and increased dietary fat lipids appeared to enhance mitochondrial dysfunction, with decreased ATP synthesis, attenuated mitochondrial gene expression, and augmented ROS generation.
Consequently, a vicious cycle occurs as these mitochondrial dysfunctions further intensify the metabolic abnormalities of the skeletal muscle. Forkhead box protein O1, IL Monocyte chemoattractant protein-1, TLR4: Toll-like receptor 4, ETC: Adapted from [ 60 ]. Dietary fat intake or overfeeding augments free fatty acid FFA supply in the liver, which can affect liver metabolism by the accumulation of intracellular lipids.
In the liver tissue, increased malonyl-CoA levels stimulate de novo FA production and prevent carnitine palmitoyltransferase-1 CPT-1 function. Consequently, fatty acids FAs cannot be broken down in the mitochondria and are diverted to other metabolic pathways, resulting in the formation of ceramides, diacylglycerol DAG , and triacylglycerol TAG [ 61 ]. In a rat model, fat-rich meal administration for only three days led to a three-fold increase in liver lipid accumulation, without any significant growth in the skeletal muscle or visceral fat content, suggesting that liver insulin resistance may precede systemic insulin resistance Figure 2 [ 62 ].
As stated above, these lipids recruit numerous inflammatory factors that derestrict insulin signaling, including the c-Jun N-terminal kinase JNK and protein kinase C PKC pathways. Additionally, in an investigational model, FFA-containing cultured hepatocytes exhibited augmented levels of prothrombotic and oxidative markers, such as nitric oxide NO , plasminogen activator inhibitor-1 PAI-1 , and malondialdehyde MDA [ 63 ].
Concurrently, massive substrate supply and liver overfeeding expose the ER to a substantial anabolic load that accordingly stimulates ER stress and protein misfolding, which can induce inflammatory signaling activation and ROS generation Figure 2 [ 61 ]. Lastly, lipid accumulation in the hepatic cells affects hepatic glucose production in impaired insulin-mediated suppression and hyperlipidemia, categorized by elevated hepatic clearance of high-density lipoprotein HDL -cholesterol combined with elevated secretion of very low-density lipoproteins VLDL [ 64 ].
In the adipose tissue, ROS production and oxidative metabolism play major roles in adipogenesis [ 65 ]. Various sources are involved in producing intracellular ROS in adipocytes. Although adipocytes are not thought to be pure energy-producing cells, ROS may be generated from electron transport chain ETC substrate overload as well as from mitochondria [ 66 ].
In adipocytes, NADPH oxidase 4 NOX4 is the core isoform and its expression is augmented in the fat cells upon exposure to enriched nutrient derivatives, including glucose or palmitate [ 67 ]. Upon intake of a meal, an inflammatory response occurs in the adipose tissue [ 69 ].
A study conducted on rat visceral adipose tissue showed that rats fed with a fatty meal showed an acute postprandial stimulation of inflammatory signaling [ 70 ]. Similarly, in humans, 6 h after the feeding of a mixed meal, a similar upregulation of MCP-1 and IL-6 was noted within the adipose tissue in normal-weight, overweight, and obese subjects, independent of the grade of adiposity Figure 2 [ 71 ]. In addition, the change in postprandial inflammatory effects in the adipose tissue due to the specific quantity and quality of dietary fat was studied by various scientific groups, but their results are conflicting.
A study involving 75 subjects with metabolic syndrome revealed that as compared to long-term ingestion of saturated fat diet, that of high-monounsaturated fat diet led to a weakened postprandial inflammatory effect in the adipose tissue [ 72 ], whereas another study indicated that individuals with metabolic syndrome displayed impaired postprandial adipose tissue inflammation, regardless of the quantity and the quality of fat ingested [ 73 ].
From the direct stimulation of inflammatory pathways by nutrient consumption, a high-fat diet may prompt native inflammation in the adipose tissue through the discharge of unnecessary FFAs. The responses of FFAs in the inflammatory pathways are facilitated through the Toll-like receptor TLR-4 , which further induces the secretion of different cytokines and macrophage aggregation in the adipose tissue Figure 2 [ 74 ]. Overall, oxidative stress can also be identified postprandially in adipocytes. In cultured adipocytes, elevated FFA levels augmented oxidative stress via NADPH oxidase stimulation, and oxidative stress directly caused dysfunctional secretion of adipokines.
Additionally, increased ROS generation caused by increased expression of NADPH oxidase and decreased expression of antioxidative enzymes was investigated in the adipose tissue of overweight mice [ 75 ]. Thus, nutrition-activated oxidative stress likely leads to a contrary native redox status that could affect the role of free radicals in the adipose tissue Figure 2 [ 76 ]. Hence, oxidative stress, induced by elevated FFA and glucose levels, insulin resistance, and long-term inflammation through the above-stated mechanisms, clearly plays a role in pancreatic cells and alters insulin secretion Figure 2 [ 16 ].
In patients with diabetes, long-term induction of plasma FFA and glucose levels has damaging effects on the pancreatic cell function [ 16 ]. An in vitro study showed that the islets or HIT-T15 cells cultured in high concentrations of FFA and glucose exhibited reduced levels of insulin mRNA and gene function and altered glucose-induced insulin secretion pathway [ 79 ].
Aberrant free radical production and oxidative stress could be one of the crucial mechanisms underlying these instabilities Figure 2. Regarding metabolic circulation, the skeletal muscle can also be characterized as a pathway controller. As a pure energy-generating organ, skeletal muscle is packed with mitochondria that control energy homeostasis.
After nutrient feeding, insulin induces glucose entry in the skeletal muscle through glucose transporter type 4 GLUT4 [ 83 ]. The capability of skeletal muscle to mainly shift from lipid oxidation and high amounts of FA utilization in fasting situations to glucose ingestion, oxidation, and storage under insulin-prompted circumstances is recognized as metabolic flexibility. The inability to shift from lipid to carbohydrate use metabolic inflexibility was investigated in obese patients and is accompanied with intra-myocellular lipid aggregation and insulin resistance Figure 2 [ 84 ].
Numerous factors regulate the metabolic flexibility of a subject, including nutrient presence, plasma FFA levels, the accessibility of the adipose tissue for lipid storage, and their level of physical activity [ 85 ]. Another factor that may be associated with metabolic flexibility is mitochondrial oxidative capability. Although a study showed contradictory data, it was suggested that mitochondrial aberrations in the muscle could stimulate metabolic flexibility to lipids and prompt insulin resistance Figure 2 [ 85 ].
In the skeletal muscle, dietary habits may also disturb physiological metabolic developments and their role through direct changes in the mitochondrial biology [ 86 ]. Together, increased dietary fat and overfeeding appeared to induce mitochondrial inactivity, with declined ATP synthesis, altered mitochondrial gene expression, and augmented ROS generation.
Consequently, a vicious cycle occurs as these mitochondrial dysfunctions further intensify the metabolic abnormalities of the skeletal muscle Figure 2. Nutrition-stimulated inflammatory and oxidative status in severe settings can alter extracellular and intracellular physiological activities. When these instabilities are recurrent, they execute a persistent inflammatory and oxidative response, which, in some cases, can prompt multiple diseases. Limited-calorie dietary patterns can provoke the precise reverse effect, promoting cell longevity and securing oxidative balance.
For instance, six months of caloric limitation significantly diminished oxidative stress and declined fasting insulin levels and body core temperature in healthy subjects [ 87 ]. Moreover, the study showed improved basal endothelial function and augmented plasma antioxidant capability in patients with diabetes, who followed a Mediterranean diet for three months in comparison with those patients on control diets [ 88 ].
Overall, evidence suggests that diet regulates oxidative stability both in an acute and in a chronic state. Nutritional variance can easily interrupt this cellular stability, initiate unfavorable pathophysiological pathways, and stimulate the incidence of numerous diseases in humans. The worldwide cancer burden is anticipated to increase by more than two-fold over the next two decades [ 89 ], therefore worsening a massive public health and medical care problem.
Physical activity, nutrition, and diet rank high among the most important risk factors for human cancer, in part because of their influences on obesity, which is a recognized risk factor for various malignancies [ 90 , 91 , 92 , 93 , 94 , 95 ]. The role of some specific nutrients in cancer etiology has been proposed based on associations stated in epidemiological studies, further supported by biological credibility.
Buy Inflammation Oxidative Stress And Cancer Dietary Approaches For Cancer Prevention
The ultimate carcinogen directly binds with a cell component probably DNA to initiate carcinogenesis. These factors are linked to the antioxidant status of selected nutrients, impact on epigenetic functions, DNA adducts, DNA repair, regulation of gene expression, inflammation, stimulation of growth factors, or influence on circulating intensities of endogenous hormones Figure 3 [ 96 , 97 , 98 ].
Incessant exposure to environmental carcinogens and inhalation chemicals is assumed to induce the amount of cytochrome P CYP1A1 expression in extrahepatic tissues via the aryl hydrocarbon receptor AhR [ 99 , , , ]. Though the latter has long been identified as a ligand-activated transcription factor TF , which is accountable for the xenobiotic inducing pathway of numerous phase I and phase II metabolizing enzymes, recent studies propose that AhR is associated with several cell signaling pathways critical to cell cycle modulation and normal homeostasis [ , ].
Alteration of these pathways is associated with tumor progression. Moreover, it is increasingly evident that P plays a vital role in the detoxification of environmental carcinogens, following the metabolic activation of dietary compounds nutrition with cancer preventative activity Figure 3 [ ].
Along with other crucial factors, such as diet, energy balance, BMI, physical activity, and metabolic rate, nutrition may also influence DNA replication of cancer cells following cancer progression. Therefore, nutrition-mediated oxidative stress plays a crucial role in carcinogenesis.
Some of the vital dietary components that have an association with oxidative stress following different aspects of carcinogenesis have been discussed in this section Table 1 and Figure 4. Nutrition as a mediator of cancer suppression at the molecular level. It directly binds to a cell component probably DNA to initiate carcinogenesis. The preventive function of nutrition can be activated by the enzymes cytochrome P in carcinogenesis. Cancer cells can form a tumor by the action of various dietary factors. Metabolically active nutritional compounds can defend carcinogenesis by suppressing the activity of carcinogen or by inducing DNA repair mechanism.
Blue colored arrows represent beneficial effect and red colored arrows represent harmful effect of nutrition [ 99 , , , ]. Some vital dietary factors have been associated with various aspects of cancer progression. Arrows represent activation of cancer and T bar represent inhibition. Alcohol is a prominent carcinogen linked with breast, oropharyngeal, colorectal, liver, and esophageal cancers [ ].
Excessive consumption of alcohol also leads to fibrotic changes in the liver [ , ]. Moreover, it leads to the production of ROS following oxidative stress, which, consequently, causes severe dysfunction and damage to the biological signaling molecules [ ]. Functional diversity in the genes associated with alcohol metabolism can result in varying exposure to the carcinogenic metabolites of alcohol; therefore, identifying genetic intolerance to alcohol can aid in cancer prognosis [ ]. For instance, people with a common genetic mutation in the alcohol dehydrogenase gene that suppresses enzyme activity have a higher risk of esophageal cancer than those who have a fully active enzyme [ ].
Alcohol facilitates its mutagenic effects by the derivation of acetaldehyde adducts, induction of the activity of Kupffer cells, and enhancing oxidative stress by augmenting formation of gut-derived endotoxins [ ]. Alcoholism results in accumulation of acetaldehyde, which, consequently, causes genotoxicity. A similar change occurs due to accumulated acetaldehyde in hepatocellular carcinoma [ , ].
Numerous epidemiological studies supported a positive interaction between breast cancer risk and alcohol [ ]. Additionally, there are several contradictory studies on the probable relationship of alcohol consumption with numerous histological grades or stages of prostate cancer [ , , , , ]. Previous meta-analyses have also emphasized these irregularities, highlighting the necessity for further studies in this area [ , ]. Carbohydrate quality could affect cancer risk, especially, that of breast cancer, significantly by influencing plasma levels of glucose and insulin, and insulin resistance [ ].
Recent meta-analysis studies described a potential relationship between glycemic index GI , degree of cancer risk, and intake of carbohydrate quality [ , , , ]. Previous studies suggest that oxidative stress may have an important role connecting acute hyperglycemia to augmented cardiovascular risk [ , , ]. Acute enhancement in blood glucose concentrations may increase the formation of free radicals by an imbalance in the ratio of NADH to NAD and by non-enzymatic glycation increased by glucose in cells [ , ].
The direct indication from studies presented that enhanced hyperglycemia or meal consumption and its derived glucose can promote oxidative stress and impair antioxidant defenses [ , ]. Consequently, oxidative stress was significantly augmented after food intake that produced a superior degree of hyperglycemia in both normal subjects and those with diabetes [ ]. Together, the potential relationship between cancer risk and dietary GI was more commonly stated by case-controls than by the cohort studies.
A probable purpose for this is that case-control reports are more liable to problems of remembering and selection difficulty than cohort studies are. In addition, most case-control studies were conducted in Europe and most cohort studies were conducted in North America. The diverse results between studies performed in North Americans and Europeans may also reveal variances in nutritional lifestyles between the two regions.
Individuals from Europe ingest carbohydrate-enriched food and different kinds of carbohydrates [ ] compared to individuals in North America [ ], who consistently consume more fats. Studies are often unable to demonstrate a relationship between oxidative stress-induced cancer risk and carbohydrate intake. Dietary lipids or fats are frequently blamed as the key source of superfluous energy.
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When caloric consumption surpasses energy expenses, the resultant substrate-induced enhancement in citric acid cycle activity produces an excess of ROS. Moreover, dietary FA ingestion influences the relative FA configuration of biological membranes defining its sensibility to oxidative changes [ ]. There are huge controversies around finding a relationship between FA-rich meals and cancer risk in population-based reports, despite a solid biological credibility underlying these relationships.
The role of inflammation in membrane fluidity and functions, stimulation of growth factors, and regulation of gene expression, or its effect on circulating levels of endogenous hormones has been cited. Recent data demonstrate a link between dietary FA with induced oxidative stress and carcinogenesis in the rat model [ ]. Several epidemiological studies mention that, rather than total dietary fat ingestion, subgroups of FAs could differentially affect cancer risk [ , , , ].
In spite of numerous studies conducted over the last decades, recent scientific data are debatable and there is a lack of reliable conclusions about the effect of EFAs and the risk of breast, bladder, colorectal, lung, or prostate cancers [ , , , ]. One of the most established mechanisms is an association between inflammatory pathways and the function of omega-3 and omega-6 FAs on the action of cyclooxygenase-2 COX-2 in prostate cancer [ , , ].
On the contrary, Gao et al. However, metabolic characteristics of these EFAs are completely conflicting. The COX-2 enzyme can convert omega-6 FAs into prostaglandin E2, a pro-inflammatory cytokine, which enables angiogenesis and cell proliferation, whereas prostaglandin E3 is produced from omega-3 FAs with the help of COX-2, which does not facilitate mitogenic characteristics [ ]. The protective action of fibers is not only associated with colorectal cancer, but also with other cancer types.
Moreover, the WCRF assessment board concluded an inadequate level of data regarding the relationship between dietary fiber and breast cancer risk [ 90 ]. Similarly, an organized review and meta-analysis of potential studies presented a significant inverse relationship between nutritional fiber intake and breast cancer risk [ ]. In addition, the recent epidemiological proof is not convincing regarding the ability of fiber intake to decrease colorectal cancer risk. Cancer initiation and progression have been associated with oxidative stress by enhancing DNA mutations or increasing DNA damage, genome variability, and cell proliferation, and hence antioxidant agents could intervene with carcinogenesis [ ].
Other flavonoid compounds, polyphenols, have anticancer activity both in humans and animal models [ , ]. Currently, increasing attention is directed towards the role of natural antioxidant agents on modulating intracellular ROS levels resulting into epigenetic alterations of essential genes in tumorigenesis [ ].
Several flavonoids were confirmed to disrupt the enzymes leading to epigenetic modifications, which regulate the inflammation process that might oscillate in cancer [ ]. Excessive ROS generation may lead to tissue injury that may induce inflammatory process [ ], the inflammatory mediators may be involved in various chronic diseases, including CVD, neurological disease, and carcinogenesis [ ]. Although in vitro studies depict a positive outcome, case-control results and phase III clinical trials afford unconvincing data for certain kinds of tumors, such as breast or prostate neoplasms [ , ].
On the contrary, according to a meta-analysis, no association was found in western women, even though these women ingested 0. Previously, studies have stated that Asian men consume high amounts of isoflavone-containing foods, while western counterparts consume mostly red meat-containing foods with minimal isoflavones [ , , ]. This variation in results can be caused by numerous factors, including dose and type of isoflavones, type of cancer, or even diverse enzymatic polymorphisms between subjects [ ].
In a nutritional diet, protein is the most important element for human health. Proteins contain no nutritional value until they are digested by protease and peptidase enzymes. Excessive protein consumption can induce amino acid oxidation and urea synthesis [ ], and impair the nutritional efficacy of energy utilization [ ]. An interesting study stated that high protein intake could obliterate the stability of antioxidants and oxidation of amino acids in the digestive system of mice and promote generation of ROS in the digestive gland [ ]. A conceivable explanation is that ROS might be generated after meat consumption during its metabolism [ ].
Moreover, high-protein ingestion can result in oxidative stress, inducing risk for long-term diseases, including carcinogenesis [ , , ]. In patients with cancer, protein consumption is decreased tremendously due to reduced digestion, low food intake, and augmented catabolism [ ]. Recently, an epidemiological study showed that intake of protein-rich food especially animal protein could be associated with a higher risk of cancer [ ]. Moreover, a few epidemiological studies have discovered an association between intake of animal protein e.
Polyphenols as Modulator of Oxidative Stress in Cancer Disease: New Therapeutic Strategies
There are no particular enduring clinical trials analyzing meatless diets for children or adults. Similarly, there is little evidence indicating that colorectal cancer progression occurs upon satisfactory consumption of animal protein [ ]. Recent epidemiological studies have been conducted to discover the association between vitamin consumption and the risk of cancer diagnosis. According to previous studies, numerous vitamins, including vitamin A, B, C, D, and E, have been implicated in the risk of cancer occurrence [ , , , , ].
Vitamins C, D, and E and selenium share fundamental antioxidant properties and all protect against oxidative stress and its harmful effects in our body that lead to carcinogenesis. However, oxidative stress is a natural process with positive outcomes, such as improved immune response [ ].
Previous studies stated that high-dose vitamin C killed cancer cells by playing a role as a pro-drug, which provides hydrogen peroxide H 2 O 2 [ , , ]. Vitamin C-induced elevated levels of ROS, including H 2 O 2 , are considered to play a vital role in carcinogenesis [ ]. Previous studies also reported that vitamin C administration promoted cytotoxicity by ATP reduction in some cancer cells [ , , ].
A case-control study involving women from Klang Valley and Selangor, Malaysia, demonstrated that a good antioxidant consumption, including vitamins A and E, can reduce oxidative stress and subsequently prevent breast cancer risk [ ]. The relationships between breast cancer and B vitamins have been broadly studied and these relationships are complex. From questionnaires, epidemiological studies have estimated an association between folate consumption and the risk of breast cancer with conflicting results [ ].
On the contrary, preventive effects have been witnessed in individuals with low folate consumption and occasional vitamin intake [ ]. Moreover, there are questionable findings for vitamin B in prostate cancer [ ], for vitamins C and E in liver [ ] and prostate cancers [ ], and for folic acid and vitamin D in pancreatic cancer [ , ].
An association between oxidative stress and cellular alteration was first recognized in when it was identified that insulin raised intracellular H 2 O 2 levels and augmented tumor cell proliferation [ ]. After more than three decades, the function of ROS in cancer progression remains conflicting. Oxidative stress is involved in various diseases, including neurodegenerative diseases [ , ], chronic inflammation [ , ], metabolic disorders [ , ], and extensively in various cancers [ , , , , ].
The rise in ROS levels from oxidative stress, as a consequence of oncogene signaling pathways, may exploit underlying mutagenesis and genomic variability in cancer cells to stimulate cancer progression. However, the effect of this excess energy generation is the accumulation of ROS, which needs to be prevented by scavenging actions to ensure cell survival [ ]. To prevent these possibly toxic effects of ROS, numerous oncogenes also augment the expression of nuclear factor erythroid 2-related factor 2 NRF2 , which diminishes ROS levels and stimulates tumorigenesis [ ].
Similarly, NRF2 not only offers protection against chemical carcinogens, but also augments cancer progression by defending cancer cells from ROS and DNA damage [ , , , , , , ]. Several studies have assessed ROS levels and generation under numerous conditions with the aim of determining when ROS are carcinogenic and when they are cancer suppressive [ ].
Moreover, ROS have been found to inversely incapacitate tumor suppressors, including protein tyrosine phosphatases PTPs and phosphatase and tensin homolog PTEN , due to the existence of the redox-sensitive cysteine residues that exist in their catalytic sites [ , , ]. Remarkably, PTPs can also control signaling pathways to induce the expression of antioxidant enzymes and diminish ROS levels [ ].
Additionally, normal stem cell renewal and differentiation are controlled by ROS levels [ ]; while cancer stem cells CSCs share similar properties with normal stem cells, comparatively little is known regarding their association with redox status. Recently, studies have shown that the liver and breast cancer stem cells tend to have low ROS levels, leading to the augmented expression of ROS-scavenging signaling proteins [ ].
Hence, although chemotherapy and radiotherapy prompt ROS generation, they are beneficial for abolishing most cancer cells, yet may be unable to cure the patient, leading to the greater capability of CSCs to endure in circumstances of high ROS by increasing antioxidants levels [ ]. As ROS are debatable mediators of the adverse effects of some anticancer drugs and ionizing radiation, CSCs may be favorably released and aggressively selected by actions that depend on increased ROS levels.
Furthermore, the supplementary oxidative stress prompted by these actions may cause further mutations and DNA damage, resulting in the expansion of drug-resistant cancer cells Figure 5. A schematic diagram of overall signaling pathways of cancer progression induced by oxidative stress. Adapted from [ ]. At elevated levels, ROS stimulate cell death and harmful cellular damage. In this case, cancer cells must overcome increased levels of ROS, particularly at initial stages of cancer progression.
Mechanisms of Carcinogenesis and Prevention Chung S. Emerging Concepts Katrina M. Wesa and Barrie R. Wiggins, and Lilian U. Sarkar Anti-Inflammatory Efficacy of Silibinin: Zimmerman, Dan Peiffer, and Gary D. Role in Breast Cancer Prevention? Dietz and Judy L. Moreau, and Tory M. Hardy and Trygve O. Ah-Ng "Tony" Kong, Ph. He is also the director for the Center for Pharmacogenetics and Pharmacogenomics at Rutgers University.
Kong has published more than original research papers, review articles, and book chapters. He has chaired and given presentations in many national and international symposia and conferences and is currently serving on the board of 15 international journals. We provide complimentary e-inspection copies of primary textbooks to instructors considering our books for course adoption.
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