The Good and Bad of Nrf2: An Update in Cancer and New Perspectives in COVID-19

Emanuele, Sonia; Celesia, Adriana; D’Anneo, Antonella; Lauricella, Marianna; Carlisi, Daniela; Blasio, Anna De; Giuliano, Michela

doi:10.3390/ijms22157963

Cited by 19 publications

(23 citation statements)

References 178 publications

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“…Nrf2 is the master regulator of the cellular antioxidant response, regulating the expression of a battery of genes encoding for antioxidant and detoxifying factors [ 71 ]. Under normal condition, kelch-like ECH-associated protein 1 (Keap1) binds Nrf2 in an inactive complex, leading to its ubiquitin-proteasomal degradation.…”

Section: Discussionmentioning

confidence: 99%

Bio-Waste Products of Mangifera indica L. Reduce Adipogenesis and Exert Antioxidant Effects on 3T3-L1 Cells

et al. 2022

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Several studies highlighted the beneficial value of natural compounds in the prevention and treatment of obesity. Here, we investigated the anti-obesity effects of extracts of peel and seed of mango (Mangifera indica L.) cultivated in Sicily (Italy) in 3T3-L1 cells. Mango Peel (MPE) and Mango Seed (MSE) extracts at a 100 µg/mL concentration significantly reduced lipid accumulation and triacylglycerol contents during 3T3-L1 adipocyte differentiation without toxicity. HPLC-ESI-MS analysis showed that both the extracts contain some polyphenolic compounds that can account for the observed biological effects. The anti-adipogenic effect of MPE and MSE was the result of down-regulation of the key adipogenic transcription factor PPARγ and its downstream targets FABP4/aP2, GLUT4 and Adipsin, as well SREBP-1c, a transcription factor which promotes lipogenesis. In addition, both MPE and MSE significantly activated AMPK with the consequent inhibition of Acetyl-CoA-carboxylase (ACC) and up-regulated PPARα. The addition of compound C, a specific AMPK inhibitor, reduced the effects of MPE and MSE on AMPK and ACC phosphorylation, suggesting a role of AMPK in mediating MPE and MSE anti-lipogenic effects. Notably, MPE and MSE possess an elevated radical scavenging activity, as demonstrated by DPPH radical scavenging assay, and reduced ROS content produced during adipocyte differentiation. This last effect could be a consequence of the increase in the antioxidant factors Nrf2, MnSOD and HO-1. In conclusion, MPE and MSE possesses both anti-adipogenic and antioxidant potential, thus suggesting that the bio-waste products of mango are promising anti-obesity natural compounds.

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Section: Discussionmentioning

confidence: 99%

Bio-Waste Products of Mangifera indica L. Reduce Adipogenesis and Exert Antioxidant Effects on 3T3-L1 Cells

et al. 2022

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“…Interestingly, chemoresistance often correlates with an increase in antioxidant activity and a reduction in intracellular ROS level [ 134 , 143 ]. In fact, many cancer cells express high levels of the transcription factor Nrf2, which increases the antioxidant defenses of the cells [ 144 , 145 ]. PN inhibits chemoresistance by inhibiting the overexpression of both Nrf2 and downstream targets, such as MnSOD and catalase [ 146 ].…”

Section: Parthenolide and Oxidative Stressmentioning

confidence: 99%

Parthenolide and Its Soluble Analogues: Multitasking Compounds with Antitumor Properties

et al. 2022

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Due to its chemical properties and multiple molecular effects on different tumor cell types, the sesquiterpene lactone parthenolide (PN) can be considered an effective drug with significant potential in cancer therapy. PN has been shown to induce either classic apoptosis or alternative caspase-independent forms of cell death in many tumor models. The therapeutical potential of PN has been increased by chemical design and synthesis of more soluble analogues including dimethylaminoparthenolide (DMAPT). This review focuses on the molecular mechanisms of both PN and analogues action in tumor models, highlighting their effects on gene expression, signal transduction and execution of different types of cell death. Recent findings indicate that these compounds not only inhibit prosurvival transcriptional factors such as NF-kB and STATs but can also determine the activation of specific death pathways, increasing intracellular reactive oxygen species (ROS) production and modifications of Bcl-2 family members. An intriguing property of these compounds is its specific targeting of cancer stem cells. The unusual actions of PN and its analogues make these agents good candidates for molecular targeted cancer therapy.

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“…Therefore, how to limit the side effects of promoting tumor growth during the application of NRF2 is also an issue that needs to be carefully considered during the study of NRF2. Some scholars believe that it is meaningful to find the transition point of NRF2 from inhibiting cancer to promoting cancer (He et al, 2020), while other scholars have proposed that inhibition of NRF2 downstream protein may attenuate the promoting effect of NRF2 on cancer cells (Cui et al, 2018;Emanuele et al, 2021). However, further research is still needed to ensure the specific mechanisms and effectiveness of these solutions.…”

Section: Drugs Related To Intestinal Fibrosismentioning

confidence: 99%

Roles of NRF2 in Fibrotic Diseases: From Mechanisms to Therapeutic Approaches

Hao

Cai

et al. 2022

Front. Physiol.

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Fibrosis is a persistent inflammatory response that causes scarring and tissue sclerosis by stimulating myofibroblasts to create significant quantities of extracellular matrix protein deposits in the tissue. Oxidative stress has also been linked to the development of fibrosis in several studies. The nuclear erythroid 2-related factor 2 (NRF2) transcription factor controls the expression of several detoxification and antioxidant genes. By binding to antioxidant response elements, NRF2 is activated by oxidative or electrophilic stress and promotes its target genes, resulting in a protective effect on cells. NRF2 is essential for cell survival under oxidative stress conditions. This review describes Kelch-like epichlorohydrin-associated protein 1 (KEAP1)/NRF2 signaling mechanisms and presents recent research advances regarding NRF2 and its involvement in primary fibrotic lesions such as pulmonary fibrosis, hepatic fibrosis, myocardial fibrosis, and renal fibrosis. The related antioxidant substances and drugs are described, along with the mechanisms by which KEAP1/NRF2 regulation positively affects the therapeutic response. Finally, the therapeutic prospects and potential value of NRF2 in fibrosis are summarized. Further studies on NRF2 may provide novel therapeutic approaches for fibrosis.

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The Good and Bad of Nrf2: An Update in Cancer and New Perspectives in COVID-19

Cited by 19 publications

References 178 publications

Bio-Waste Products of Mangifera indica L. Reduce Adipogenesis and Exert Antioxidant Effects on 3T3-L1 Cells

Bio-Waste Products of Mangifera indica L. Reduce Adipogenesis and Exert Antioxidant Effects on 3T3-L1 Cells

Parthenolide and Its Soluble Analogues: Multitasking Compounds with Antitumor Properties

Roles of NRF2 in Fibrotic Diseases: From Mechanisms to Therapeutic Approaches

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