Cell‑specific and roasting‑dependent regulation of the Keap1/Nrf2 pathway by coffee extracts

Priftis, Alexandros; Angeli‐Terzidou, Antonia‐Eugenia; Veskoukis, Aristidis S.; Spandidos, Demetrios Α.; Kouretas, Demetrios

doi:10.3892/mmr.2018.8924

Cited by 13 publications

(14 citation statements)

References 38 publications

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“…The OO extracts were selected for further analysis in order to shed light on olive oils' mechanism of action. Based on the literature, polyphenols are able to cause Nrf2 detachment from the cytosol-localized Keap1 and subsequent translocation to the nucleus followed by antioxidant gene expression [30, 31]. The OO extracts were administered in HeLa cells at concentrations that caused the maximum increase in GSH levels and sequentially were assessed for their effect on gene expression levels of Nrf2 target genes by qPCR.…”

Section: Resultsmentioning

confidence: 99%

“…The expression of all the aforementioned genes is subject to regulation by an antioxidant response element (ARE) in their promoter region, recognized by the Nrf2. These proteins are a part of the complex antioxidant machinery that protects cells from oxidative impairments by neutralizing ROS [31]. Therefore, extracts or compounds that upregulate their expression may be used as potential antioxidant supplements.…”

Section: Resultsmentioning

confidence: 99%

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The Polyphenolic Composition of Extracts Derived from Different Greek Extra Virgin Olive Oils Is Correlated with Their Antioxidant Potency

Kouka

Tsakiri

Tzortzi

et al. 2019

Oxidative Medicine and Cellular Longevity

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Olive oil possesses a predominant role in the diet of countries around the Mediterranean basin, whereas it is a known constituent of several sectors of human culture. The polyphenolic composition of olive oil seems to be a key factor in its beneficial biological properties. Based on the above, the aim of this study was to correlate the polyphenolic composition of five extracts derived from a Greek olive oil variety with their antioxidant potency and antimutagenic activities in vitro with chemical-based techniques and cell culture-based assays. According to the results obtained, the polyphenol samples with higher concentration of hydroxytyrosol (HT) were more potent in antioxidant and antimutagenic activity in vitro, as indicated by their ability to scavenge ABTS⋅+ radical and to protect the strand of plasmid DNA from free radical-induced breaking compared to the corresponding samples with higher levels of tyrosol (T) and its derivatives. However, this observation was not evident in the cell culture model (i.e., the HeLa cervical cancer cell line) to which the tested extracts were administered. Specifically, the T-rich extracts more effectively increased endogenous GSH levels measured by flow cytometry than did the HT-rich compounds. Also, olive oil compounds contributed variously to the expression of genes implicated in the cell antioxidant machinery, as indicated by quantitative PCR. Therefore, the relationship between structure and function in redox regulation is complex and merits the combination of tests. Given that factors like the production and storage regimen of the plants are major determinants of the composition of the generated extracts, we propose that specific conditions should be adopted in order to achieve their maximum biological activity. These results followed by others in the same direction could provide a solid basis for the production of functional foods enriched in olive oil extracts with potential antioxidant action in vivo.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

The Polyphenolic Composition of Extracts Derived from Different Greek Extra Virgin Olive Oils Is Correlated with Their Antioxidant Potency

Kouka

Tsakiri

Tzortzi

et al. 2019

Oxidative Medicine and Cellular Longevity

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“…After exposure to several redox altering stimuli, highly reactive thiols of KEAP1 are subjected to instant modification, leading to NRF2 stabilization caused by its decreased affinity for the CUL3-KEAP1 complex. Subsequently, NRF2 translocates into the nucleus and binds to the antioxidant response element (ARE) located within the promoter region of specific target genes, inducing the expression of a large number of cytoprotective proteins with antioxidant and detoxifying roles [2][3][4][5]. The importance of NRF2 function has been demonstrated by several studies using NRF2-deficient mice showing an increased susceptibility to redox disturbances and xenobiotic stress [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Potential Applications of NRF2 Modulators in Cancer Therapy

et al. 2020

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The nuclear factor erythroid 2-related factor 2 (NRF2)–Kelch-like ECH-associated protein 1 (KEAP1) regulatory pathway plays an essential role in protecting cells and tissues from oxidative, electrophilic, and xenobiotic stress. By controlling the transactivation of over 500 cytoprotective genes, the NRF2 transcription factor has been implicated in the physiopathology of several human diseases, including cancer. In this respect, accumulating evidence indicates that NRF2 can act as a double-edged sword, being able to mediate tumor suppressive or pro-oncogenic functions, depending on the specific biological context of its activation. Thus, a better understanding of the mechanisms that control NRF2 functions and the most appropriate context of its activation is a prerequisite for the development of effective therapeutic strategies based on NRF2 modulation. In line of principle, the controlled activation of NRF2 might reduce the risk of cancer initiation and development in normal cells by scavenging reactive-oxygen species (ROS) and by preventing genomic instability through decreased DNA damage. In contrast however, already transformed cells with constitutive or prolonged activation of NRF2 signaling might represent a major clinical hurdle and exhibit an aggressive phenotype characterized by therapy resistance and unfavorable prognosis, requiring the use of NRF2 inhibitors. In this review, we will focus on the dual roles of the NRF2-KEAP1 pathway in cancer promotion and inhibition, describing the mechanisms of its activation and potential therapeutic strategies based on the use of context-specific modulation of NRF2.

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“…The observed responses could be mainly attributed, at the molecular level, to specific transcription factors, namely, NF- κ B, p38 MAPK, members of the FoxO family, and nuclear factor erythroid-derived 2-like 2 (Nrf2) all activated by low ROS levels [ 38 , 39 ]. Focusing on Nrf2, it has been suggested that it is critical for the regulation of the intracellular redox status [ 40 , 41 ]. It acts by promoting both constitutive and inducible expressions of the antioxidant response element- (ARE-) regulated genes, which code for numerous antioxidant metabolites and enzymes [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Exercise‐Induced Reductive Stress Is a Protective Mechanism against Oxidative Stress in Peripheral Blood Mononuclear Cells

Spanidis

Veskoukis

Papanikolaou

et al. 2018

Oxidative Medicine and Cellular Longevity

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Eccentric exercise is a well-studied modality that induces oxidative stress and muscle damage. Furthermore, it promotes inflammatory response in which peripheral blood mononuclear cells (PBMCs) are the major mediators. Although free radicals are necessary in a specific range of concentrations, yet unknown, it remains unclear whether reductive redox status (i.e., increased antioxidant defenses and impaired free radical generation) is beneficial or not. Thus, the aim of the present investigation was to examine the effects of reductive stress and the impact of reduced glutathione (GSH) baseline values on the ability of PBMCs to counteract oxidative stress induced by a potent oxidative agent. PBMCs were isolated from the blood of subjects who performed eccentric exercise and treated with t-BOOH for 24 h. The subjects were clustered in the reductive and the oxidative group on the basis of increased or decreased GSH concentration postexercise compared to preexercise values, respectively. According to our results in PBMCs, lipid peroxidation levels as depicted by thiobarbituric acid reactive substances (TBARS) remained unchanged in the reductive group contrary to the observed enhancement in the oxidative group. In addition, GSH concentration and catalase activity increased in the reductive group, whereas they were not affected in the oxidative group. In conclusion, the effects of an oxidizing agent on the redox status of PBMCs isolated from the blood of athletes after acute eccentric exercise are dependent on the baseline values of GSH in erythrocytes. Otherwise, reductive stress defined by increased GSH levels is a protective mechanism, at least when followed by an oxidative stimulus.

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Cell‑specific and roasting‑dependent regulation of the Keap1/Nrf2 pathway by coffee extracts

Cited by 13 publications

References 38 publications

The Polyphenolic Composition of Extracts Derived from Different Greek Extra Virgin Olive Oils Is Correlated with Their Antioxidant Potency

The Polyphenolic Composition of Extracts Derived from Different Greek Extra Virgin Olive Oils Is Correlated with Their Antioxidant Potency

Potential Applications of NRF2 Modulators in Cancer Therapy

Exercise‐Induced Reductive Stress Is a Protective Mechanism against Oxidative Stress in Peripheral Blood Mononuclear Cells

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