Controversy about pharmacological modulation of Nrf2 for cancer therapy

Milković, Lidija; Žarković, Neven; Saso, Luciano

doi:10.1016/j.redox.2017.04.013

Cited by 119 publications

(96 citation statements)

References 58 publications

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“…[ 57 ] Nrf2 is another transcription factor discussed being a tumor promotor and suppressor at the same time. [ 58 ] Nrf2 translocation to the nucleus was increased with MMC and MTX as well as plasma treatment in tendency and regulates the transcription of antioxidant and anti‐apoptotic genes. [ 59 ] The increased translocation of Nrf2 was likely due to its redox‐sensitive activation upstream.…”

Section: Discussionmentioning

confidence: 99%

Medical Gas Plasma Jet Technology Targets Murine Melanoma in an Immunogenic Fashion

et al. 2020

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Medical technologies from physics are imperative in the diagnosis and therapy of many types of diseases. In 2013, a novel cold physical plasma treatment concept was accredited for clinical therapy. This gas plasma jet technology generates large amounts of different reactive oxygen and nitrogen species (ROS). Using a melanoma model, gas plasma technology is tested as a novel anticancer agent. Plasma technology derived ROS diminish tumor growth in vitro and in vivo. Varying the feed gas mixture modifies the composition of ROS. Conditions rich in atomic oxygen correlate with killing activity and elevate intratumoral immune‐infiltrates of CD8+ cytotoxic T‐cells and dendritic cells. T‐cells from secondary lymphoid organs of these mice stimulated with B16 melanoma cells ex vivo show higher activation levels as well. This correlates with immunogenic cancer cell death and higher calreticulin and heat‐shock protein 90 expressions induced by gas plasma treatment in melanoma cells. To test the immunogenicity of gas plasma treated melanoma cells, 50% of mice vaccinated with these cells are protected from tumor growth compared to 1/6 and 5/6 mice negative control (mitomycin C) and positive control (mitoxantrone), respectively. Gas plasma jet technology is concluded to provide immunoprotection against malignant melanoma both in vitro and in vivo.

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Section: Discussionmentioning

confidence: 99%

Medical Gas Plasma Jet Technology Targets Murine Melanoma in an Immunogenic Fashion

et al. 2020

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“…Following the ROS pattern, growth on collagen increased NRF2 levels, and HNE treatments additionally increased NRF2 on native collagen and collagen pretreated with 10 µM of HNE. HNE is known to activate NRF2 by releasing it from KEAP1 inhibition, and once NRF2 is freed, it translocates to the nucleus [20]. In the nucleus, NRF2 activates transcription of antioxidant genes, among which are glutamate-cysteine ligase, catalytic subunit, and glutamate-cysteine ligase, a modifier subunit, and an enzyme which catalyzes the first step in GSH synthesis [20].…”

Section: Discussionmentioning

confidence: 99%

Chronic Oxidative Stress Promotes Molecular Changes Associated with Epithelial Mesenchymal Transition, NRF2, and Breast Cancer Stem Cell Phenotype

et al. 2019

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Oxidative stress plays a role in carcinogenesis, but it also contributes to the modulation of tumor cells and microenvironment caused by chemotherapeutics. One of the consequences of oxidative stress is lipid peroxidation, which can, through reactive aldehydes such as 4-hydroxy-2-nonenal (HNE), affect cell signaling pathways. On the other hand, cancer stem cells (CSC) are now recognized as a major factor of malignancy by causing metastasis, relapse, and therapy resistance. Here, we evaluated whether oxidative stress and HNE modulation of the microenvironment can influence CSC growth, modifications of the epithelial to mesenchymal transition (EMT) markers, the antioxidant system, and the frequency of breast cancer stem cells (BCSC). Our results showed that oxidative changes in the microenvironment of BCSC and particularly chronic oxidative stress caused changes in the proliferation and growth of breast cancer cells. In addition, changes associated with EMT, increase in glutathione (GSH) and Nuclear factor erythroid 2-related factor 2 (NRF2) were observed in breast cancer cells grown on HNE pretreated collagen and under chronic oxidative stress. Our results suggest that chronic oxidative stress can be a bidirectional modulator of BCSC fate. Low levels of HNE can increase differentiation markers in BCSC, while higher levels increased GSH and NRF2 as well as certain EMT markers, thereby increasing therapy resistance.

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“…D. Nuclear Factor (Erythroid-Derived 2)-Like 2 Inhibitors NRF2 has a "dark side" related to its oncogenic activity when constitutively and highly overexpressed. Therefore, NRF2 inhibition has been proposed as a mechanism to sensitize cancer cells to chemotherapeutic drugs or radiotherapy (Milkovic et al, 2017). Two strategies can be envisioned to inhibit NRF2 with small molecules: PPI inhibitors that disrupt the bZip interaction between NRF2 and MAFs, and DNA-protein interaction inhibitors that block binding of NRF2-MAF to the ARE (Fig.…”

Section: B Protein-protein Interaction Inhibitors For Nuclear Factormentioning

confidence: 99%

Transcription Factor NRF2 as a Therapeutic Target for Chronic Diseases: A Systems Medicine Approach

et al. 2018

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Controversy about pharmacological modulation of Nrf2 for cancer therapy

Cited by 119 publications

References 58 publications

Medical Gas Plasma Jet Technology Targets Murine Melanoma in an Immunogenic Fashion

Medical Gas Plasma Jet Technology Targets Murine Melanoma in an Immunogenic Fashion

Chronic Oxidative Stress Promotes Molecular Changes Associated with Epithelial Mesenchymal Transition, NRF2, and Breast Cancer Stem Cell Phenotype

Transcription Factor NRF2 as a Therapeutic Target for Chronic Diseases: A Systems Medicine Approach

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