Molecular mechanisms linking environmental toxicants to cancer development: Significance for protective interventions with polyphenols

Lagoa, Ricardo; Marques‐da‐Silva, Dorinda; Diniz, Mário; Daglia, Maria; Bishayee, Anupam

doi:10.1016/j.semcancer.2020.02.002

Cited by 29 publications

(39 citation statements)

References 341 publications

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“…In particular, β-HCH was found to exert its carcinogenicity by means of several mechanisms: modulation of STAT3-mediated oncogenic pathways, AhR activation, disruption of AR signaling cascade, establishment of oxidative stress and induction of genotoxic responses [ 17 , 18 , 19 ]. The first line of defense against external insults could be a green therapeutic plan providing for the exploitation of natural bioactive compounds to counteract pollutants toxicity [ 69 , 70 ]. Scientific literature gave positive evidence regarding the bioactivity of natural-derived products, which show great structural diversity and elicit a wide range of biological effects.…”

Section: Discussionmentioning

confidence: 99%

Tomato and Olive Bioactive Compounds: A Natural Shield against the Cellular Effects Induced by β-Hexachlorocyclohexane-Activated Signaling Pathways

et al. 2021

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The β-isomer of hexachlorocyclohexane (β-HCH) is a globally widespread pollutant that embodies all the physicochemical characteristics of organochlorine pesticides, constituting an environmental risk factor for a wide range of noncommunicable diseases. Previous in vitro studies from our group disclosed the carcinogenic potential of β-HCH, which contributes to neoplastic transformation by means of multifaceted intracellular mechanisms. Considering the positive evidence regarding the protective role of natural bioactive compounds against pollution-induced toxicity, micronutrients from olive and tomato endowed with the capability of modulating β-HCH cellular targets were tested. For this purpose, the solution obtained from a patented food supplement (No. EP2851080A1), referred to as Tomato and Olive Bioactive Compounds (TOBC), was administered to the androgen-sensitive prostate cancer cells LNCaP and different biochemical and cellular assays were performed to evaluate its efficiency. TOBC shows a dose-dependent significant chemoprotection by contrasting β-HCH-induced intracellular responses such as STAT3 and AhR activation, disruption of AR signaling, antiapoptotic and proliferative activity, and increase in ROS production and DNA damage. These experimental outcomes identified TOBC as a suitable functional food to be included in a diet regimen aimed at defending cells from β-HCH negative effects, recommending the development of tailored enriched formulations for exposed individuals.

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Section: Discussionmentioning

confidence: 99%

Tomato and Olive Bioactive Compounds: A Natural Shield against the Cellular Effects Induced by β-Hexachlorocyclohexane-Activated Signaling Pathways

et al. 2021

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“…Of note, low doses of Cd in the water administered to mice increased oxidative stress markers and affected mitochondrial respiration and lipid metabolism in the lungs [ 44 ]. Significant increases in the expression of pro-inflammatory genes (NF-kB and COX-1) were also described in the liver and kidney of mice treated with cadmium chloride [ 8 ].…”

Section: Cadmium-associated Cardiotoxicity Via Lipid Metabolismmentioning

confidence: 99%

Misuse of Cardiac Lipid upon Exposure to Toxic Trace Elements—A Focused Review

et al. 2022

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Heavy metals and metalloids like cadmium, arsenic, mercury, and lead are frequently found in the soil, water, food, and atmosphere; trace amounts can cause serious health issues to the human organism. These toxic trace elements (TTE) affect almost all the organs, mainly the heart, kidney, liver, lungs, and the nervous system, through increased free radical formation, DNA damage, lipid peroxidation, and protein sulfhydryl depletion. This work aims to advance our understanding of the mechanisms behind lipid accumulation via increased free fatty acid levels in circulation due to TTEs. The increased lipid level in the myocardium worsens the heart function. This dysregulation of the lipid metabolism leads to damage in the structure of the myocardium, inclusive fibrosis in cardiac tissue, myocyte apoptosis, and decreased contractility due to mitochondrial dysfunction. Additionally, it is discussed herein how exposure to cadmium decreases the heart rate, contractile tension, the conductivity of the atrioventricular node, and coronary flow rate. Arsenic may induce atherosclerosis by increasing platelet aggregation and reducing fibrinolysis, as exposure interferes with apolipoprotein (Apo) levels, resulting in the rise of the Apo-B/Apo-A1 ratio and an elevated risk of acute cardiovascular events. Concerning mercury and lead, these toxicants can cause hypertension, myocardial infarction, and carotid atherosclerosis, in association with the generation of free radicals and oxidative stress. This review offers a complete overview of the critical factors and biomarkers of lipid and TTE-induced cardiotoxicity useful for developing future protective interventions.

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“…Polyphenols such as anthocyanins can stimulate NRF2-mediated antioxidant gene expression and augment cellular and organismal resistance to stressors, either internal, such as metabolic stress and aging, or external, such as pollutants and UV radiation (Son, Camandola, and Mattson 2008;Leri et al 2020). In fact, there is evidence that anthocyanins and oligomeric procyanidins protect the skin against UV-B damage (Li et al 2019, Saliou et al 2001, that they lower systemic oxidative stress (Ullah et al 2019), and that they protect against various kinds of environmental pollutants (Lagoa et al 2020).…”

Section: Berries For Dietary Geroprotectionmentioning

confidence: 99%

Biomarkers of geroprotection and cardiovascular health: An overview of omics studies and established clinical biomarkers in the context of diet

Secci

Hartmann

Walter

et al. 2021

Critical Reviews in Food Science and Nutrition

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Molecular mechanisms linking environmental toxicants to cancer development: Significance for protective interventions with polyphenols

Cited by 29 publications

References 341 publications

Tomato and Olive Bioactive Compounds: A Natural Shield against the Cellular Effects Induced by β-Hexachlorocyclohexane-Activated Signaling Pathways

Tomato and Olive Bioactive Compounds: A Natural Shield against the Cellular Effects Induced by β-Hexachlorocyclohexane-Activated Signaling Pathways

Misuse of Cardiac Lipid upon Exposure to Toxic Trace Elements—A Focused Review

Biomarkers of geroprotection and cardiovascular health: An overview of omics studies and established clinical biomarkers in the context of diet

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