Overview on Oxidative Stress, Inflammation, Cancer Initiation/Progression, and How to Prevent Carcinogenesis/Cancer

Background Oxidative stress (OS) is a key characteristic feature in cancer initiation and progression. Among multiple cancers, NADPH oxidase (NOX) dependent free radical production is implicated in oxidative stress. P22phox, a subunit of NADPH oxidase encoded by the CYBA gene has functional polymorphisms associated with various complex diseases. The present study was aimed to examine the importance and association of the functional polymorphisms of CYBA gene (-930 A/G and 242 C/T) with the oxidative stress in breast cancer (BC) development and progression. Materials and Methods We have performed a case-control study on 300 breast cancer patients and 300 healthy individuals as controls to examine the role of CYBA gene -930 A/G and 242 C/T single nucleotide polymorphisms (SNPs) using As-PCR and PCR-RFLP assays and its association with OS as measured by plasma MDA levels. Linkage disequilibrium (LD) plots were generated using Haploviewtool and Multifactor dimensionality reduction (MDR) analysis was applied to assess high-order interactions between the SNPs. The Insilco analysis has been performed to predict the effect of SNPs on the gene regulation using online tools. Results We have found that genotype frequencies of CYBA gene -930 A/G and 242C/T polymorphism were significantly different between controls and BC patients (p < 0.05). The haplotype combination -930G/242C and -930G/242T were associated with 1.44 & 1.56 folds increased risk for breast cancer respectively. Further, the MDA levels were higher in the patients carrying -930G/242C and -930G/242T haplotype (p < 0.001). Our results have been substantiated by Insilco analysis. Conclusion Results of the present study suggest that GG genotype of -930 A/G polymorphism, -930G/242C and -930G/242T haplotypes of CYBA gene polymorphisms have shown association with higher MDA levels in breast cancer patients, signify that elevated oxidative stress might aid in increased risk for breast cancer initiation and progression.

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Correlation between Oxidative Stress, Nutrition, and Cancer Initiation

International Journal of Molecular Sciences ◽

10.3390/ijms18071544 ◽

2017 ◽

Vol 18 (7) ◽

pp. 1544 ◽

Cited By ~ 92

Author(s):

Subbroto Kumar Saha ◽

Soo Bin Lee ◽

Jihye Won ◽

Hye Yeon Choi ◽

Kyeongseok Kim ◽

...

Keyword(s):

Oxidative Stress ◽

Cancer Initiation

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Miracle Berry as a Potential Supplement in the Control of Metabolic Risk Factors in Cancer

Antioxidants ◽

10.3390/antiox9121282 ◽

2020 ◽

Vol 9 (12) ◽

pp. 1282

Author(s):

Marta Gómez de Cedrón ◽

Sonia Wagner ◽

Marina Reguero ◽

Adrián Menéndez-Rey ◽

Ana Ramírez de Molina

Keyword(s):

Oxidative Stress ◽

Risk Factors ◽

Insulin Resistance ◽

Chronic Diseases ◽

Sweet Taste ◽

Low Grade ◽

Taste Receptors ◽

Sweet Taste Receptors ◽

Cancer Initiation ◽

Altered Metabolism

The increased incidence of chronic diseases related to altered metabolism has become a social and medical concern worldwide. Cancer is a chronic and multifactorial disease for which, together with genetic factors, environmental factors are crucial. According to the World Health Organization (WHO), up to one third of cancer-related deaths could be prevented by modifying risk factors associated with lifestyle, including diet and exercise. Obesity increases the risk of cancer due to the promotion of low-grade chronic inflammation and systemic metabolic oxidative stress. The effective control of metabolic parameters, for example, controlling glucose, lipid levels, and blood pressure, and maintaining a low grade of chronic inflammation and oxidative stress might represent a specific and mechanistic approach against cancer initiation and progression. Miracle berry (MB) (Synsepalum dulcificum) is an indigenous fruit whose small, ellipsoid, and bright red berries have been described to transform a sour taste into a sweet one. MB is rich in terpenoids, phenolic compounds, and flavonoids, which are responsible for their described antioxidant activities. Moreover, MB has been reported to ameliorate insulin resistance and inhibit cancer cell proliferation and malignant transformation in vitro. Herein, we briefly summarize the current knowledge of MB to provide a scientific basis for its potential use as a supplement in the management of chronic diseases related to altered metabolism, including obesity and insulin resistance, which are well-known risk factors in cancer. First, we introduce cancer as a metabolic disease, highlighting the impact of systemic metabolic alterations, such as obesity and insulin resistance, in cancer initiation and progression. Next, as oxidative stress is closely associated with metabolic stress, we also evaluate the effect of phytochemicals in managing oxidative stress and its relationship with cancer. Finally, we summarize the main biological activities described for MB-derived extracts with a special focus on the ability of miraculin to transform a sour taste into a sweet one through its interaction with the sweet taste receptors. The identification of sweet taste receptors at the gastrointestinal level, with effects on the secretion of enterohormones, may provide an additional tool for managing chronic diseases, including cancer.

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Amelioration of oxidative stress, inflammation and liver function by nutraceuticals in rat model of hepatic cancer initiation induced by N-nitrosodiethylamine

Journal of Herbmed Pharmacology ◽

10.34172/jhp.2021.21 ◽

2021 ◽

Vol 10 (2) ◽

pp. 194-201

Author(s):

Sahar Y. Al-Okbi ◽

Doha A. Mohamed ◽

Hagar F.H. Elbakry

Keyword(s):

Oxidative Stress ◽

Liver Cancer ◽

Total Protein ◽

Catalase Activity ◽

The Other ◽

Dna Integrity ◽

Protective Agent ◽

Tnf Α ◽

Cancer Initiation ◽

High Oxidative Stress

Introduction: Nutraceuticals might serve as protective agent against liver cancer induced by pro-cancerous chemicals that initiate high oxidative stress, inflammation and affect DNA integrity. The aim of the present research was to study the prevention of hepatocellular carcinoma initiation induced by N-nitrosodiethylamine (NDEA) through treatment by nutraceuticals. Methods: Two nutraceuticals were prepared; the first (NI) was a mixture of different extracts of green tea, wheat germ and tomato, the second one (NII) was composed of extracts mixture of broccoli, hazelnuts and carrot. Total flavonoids and flavonols were determined in the nutraceuticals. Four groups of rats were run; the first served as control normal, the other three groups were treated by intraperitoneal injection of NDEA, one of these groups was designated as control NDEA, the other two groups (test groups) were treated daily with oral doses of NI and NII, respectively. The experiment continued for 8 weeks. Plasma transaminases, alkaline phosphatase and catalase activities, total protein, albumin, malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α) along with liver MDA level and catalase activity were assessed. Results: NI showed higher flavonoids and lower flavonols than NII (P < 0.05). High oxidative stress and inflammation biomarkers, liver dysfunction, reduced plasma albumin and total protein were demonstrated in control NDEA compared to control normal (P < 0.05). Test groups showed significant improvement in all parameters (P < 0.05) compared to NDEA control. NI was superior in improving plasma transaminases and catalase activities, MDA and TNF-α levels and liver catalase activity compared to NII (P < 0.05). Conclusion: Both NI and NII might prevent liver cancer initiation during exposure to carcinogenic agents, NI being superior to NII.

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Oxidative Stress in the Metabolism of Estrogens Leading to Cancer Initiation: Prevention by Specific Antioxidants

ACS Symposium Series - Oxidative Stress: Diagnostics, Prevention, and Therapy ◽

10.1021/bk-2011-1083.ch004 ◽

2011 ◽

pp. 83-98

Author(s):

Eleanor G. Rogan ◽

Ercole L. Cavalieri

Keyword(s):

Oxidative Stress ◽

Cancer Initiation

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Abstract 2356: Pro-inflammatory macrophages promote prostate cancer initiation and progression via NOX2-mediated oxidative stress

10.1158/1538-7445.am2015-2356 ◽

2015 ◽

Cited By ~ 1

Author(s):

Kia J. Jones ◽

Latoya K. Bryant ◽

Cimona V. Hinton

Keyword(s):

Oxidative Stress ◽

Prostate Cancer ◽

Cancer Initiation ◽

Inflammatory Macrophages

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Lycopene alleviates sulfamethoxazole-induced hepatotoxicity in grass carp (Ctenopharyngodon idellus) via suppression of oxidative stress, inflammation and apoptosis

Food & Function ◽

10.1039/d0fo01638a ◽

2020 ◽

Vol 11 (10) ◽

pp. 8547-8559

Author(s):

Hongjing Zhao ◽

Yu Wang ◽

Mengyao Mu ◽

Menghao Guo ◽

Hongxian Yu ◽

...

Keyword(s):

Oxidative Stress ◽

Secondary Metabolites ◽

Human Health ◽

Grass Carp ◽

Aquatic Environment ◽

Ctenopharyngodon Idellus

Antibiotics are used worldwide to treat diseases in humans and other animals; most of them and their secondary metabolites are discharged into the aquatic environment, posing a serious threat to human health.

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Copper-dependent ATP7B up-regulation drives the resistance of TMEM16A-overexpressing head-and-neck cancer models to platinum toxicity

Biochemical Journal ◽

10.1042/bcj20190591 ◽

2019 ◽

Vol 476 (24) ◽

pp. 3705-3719 ◽

Cited By ~ 2

Author(s):

Avani Vyas ◽

Umamaheswar Duvvuri ◽

Kirill Kiselyov

Keyword(s):

Oxidative Stress ◽

Head And Neck ◽

Transcriptional Activation ◽

Platinum Resistance ◽

Mrna Levels ◽

Strong Positive Correlation ◽

Platinum Compounds ◽

Copper Chelation ◽

Novel Approach ◽

Cancer Models

Platinum-containing drugs such as cisplatin and carboplatin are routinely used for the treatment of many solid tumors including squamous cell carcinoma of the head and neck (SCCHN). However, SCCHN resistance to platinum compounds is well documented. The resistance to platinum has been linked to the activity of divalent transporter ATP7B, which pumps platinum from the cytoplasm into lysosomes, decreasing its concentration in the cytoplasm. Several cancer models show increased expression of ATP7B; however, the reason for such an increase is not known. Here we show a strong positive correlation between mRNA levels of TMEM16A and ATP7B in human SCCHN tumors. TMEM16A overexpression and depletion in SCCHN cell lines caused parallel changes in the ATP7B mRNA levels. The ATP7B increase in TMEM16A-overexpressing cells was reversed by suppression of NADPH oxidase 2 (NOX2), by the antioxidant N-Acetyl-Cysteine (NAC) and by copper chelation using cuprizone and bathocuproine sulphonate (BCS). Pretreatment with either chelator significantly increased cisplatin's sensitivity, particularly in the context of TMEM16A overexpression. We propose that increased oxidative stress in TMEM16A-overexpressing cells liberates the chelated copper in the cytoplasm, leading to the transcriptional activation of ATP7B expression. This, in turn, decreases the efficacy of platinum compounds by promoting their vesicular sequestration. We think that such a new explanation of the mechanism of SCCHN tumors’ platinum resistance identifies novel approach to treating these tumors.

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Clinical aspects of reactive oxygen and nitrogen species

Biochemical Society Symposium ◽

10.1042/bss0710121 ◽

2004 ◽

Vol 71 ◽

pp. 121-133 ◽

Cited By ~ 25

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.

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