Recent Advances of Gold Compounds in Anticancer Immunity

Yue, Shuang; Luo, Miao; Liu, Huiguo; Wei, Shuang

doi:10.3389/fchem.2020.00543

Cited by 56 publications

(48 citation statements)

References 114 publications

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“…Intriguingly, the mechanisms by which these compounds inhibit inflammation was largely unknown at the time they were adopted for clinical use. Subsequent investigation of gold compounds for alternative indications, including lung disease and cancer, have revealed the involvement of both NRF2 and NFκB pathways [ 17 ]. Thus, the NFκB pathway, as a key regulator of inflammation, represents an intersection between antioxidant and anti-inflammatory pathways modulated by NRF2.…”

Section: Discussionmentioning

confidence: 99%

Auranofin-Mediated NRF2 Induction Attenuates Interleukin 1 Beta Expression in Alveolar Macrophages

Wall

Butler

et al. 2021

Antioxidants

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Background: Alveolar macrophages (AMs) are resident inflammatory cells in the lung that serve as early sentinels of infection or injury. We have identified thioredoxin reductase 1 inhibition by gold compounds increases activation of nuclear factor erythroid 2-related factor 2 (NRF2)-dependent pathways to attenuate inflammatory responses. The present studies utilized murine alveolar macrophages (MH-S) to test the hypothesis that the gold compound, auranofin (AFN), decreases interleukin (IL)-1β expression through NRF2-mediated interactions with nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway genes and/or increases in glutathione synthesis. Methods: MH-S cells were treated with AFN and lipopolysaccharide (LPS) and analyzed at 6 and 24 h. The Il1b promoter was analyzed by chromatin immunoprecipitation for direct interaction with NRF2. Results: Expression of IL-1β, p-IκBα, p-p65 NF-kB, and NOD-, LRR-, and pyrin domain-containing protein 3 were elevated by LPS exposure, but only IL-1β expression was suppressed by AFN treatment. Both AFN and LPS treatments increased cellular glutathione levels, but attenuation of glutathione synthesis by buthionine sulfoximine (BSO) did not alter expression of Il-1β. Analysis revealed direct NRF2 binding to the Il1b promoter which was enhanced by AFN and inhibited the transcriptional activity of DNA polymerase II. Conclusions: Our data demonstrate that AFN-induced NRF2 activation directly suppresses IL-1β synthesis independent of NFκB and glutathione-mediated antioxidant mechanisms. NRF2 binding to the promoter region of IL1β directly inhibits transcription of the IL1β gene. Collectively, our research suggests that gold compounds elicit NRF2-dependent pulmonary protection by suppressing macrophage-mediated inflammation.

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Section: Discussionmentioning

confidence: 99%

Auranofin-Mediated NRF2 Induction Attenuates Interleukin 1 Beta Expression in Alveolar Macrophages

Wall

Butler

et al. 2021

Antioxidants

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“…These 'alarm' molecules, also known as danger signals, alarmins, or more precisely damage-associated molecular patterns (DAMPs), makes such type of apoptotic cell death 'immunogenic' because they promote an inflammatory response. DAMPs attract innate immune cells, especially antigen presenting cells (APCs) such as dendritic cells, leading to the phagocytosis of the dying cells followed by transportation to the lymphatics where tumor antigens are presented to T cells [9,116,[120][121][122][123]. The most critical DAMPs released during ICD are calreticulin (CLR), ATP, and high-mobility group box 1 (HMGB1) protein [124].…”

Section: New Viewpoint Of Research With Auranofin Against Cancer: the Link With Platinum-based Chemotherapy Immunogenic Cell Death And Immentioning

confidence: 99%

The gold complex auranofin: new perspectives for cancer therapy

Abdalbari

Telleria

2021

Discov Onc

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Advanced stages of cancer are highly associated with short overall survival in patients due to the lack of long-term treatment options following the standard form of care. New options for cancer therapy are needed to improve the survival of cancer patients without disease recurrence. Auranofin is a clinically approved agent against rheumatoid arthritis that is currently enrolled in clinical trials for potential repurposing against cancer. Auranofin mainly targets the anti-oxidative system catalyzed by thioredoxin reductase (TrxR), which protects the cell from oxidative stress and death in the cytoplasm and the mitochondria. TrxR is over-expressed in many cancers as an adaptive mechanism for cancer cell proliferation, rendering it an attractive target for cancer therapy, and auranofin as a potential therapeutic agent for cancer. Inhibiting TrxR dysregulates the intracellular redox state causing increased intracellular reactive oxygen species levels, and stimulates cellular demise. An alternate mechanism of action of auranofin is to mimic proteasomal inhibition by blocking the ubiquitin–proteasome system (UPS), which is critically important in cancer cells to prevent cell death when compared to non-cancer cells, because of its role on cell cycle regulation, protein degradation, gene expression, and DNA repair. This article provides new perspectives on the potential mechanisms used by auranofin alone, in combination with diverse other compounds, or in combination with platinating agents and/or immune checkpoint inhibitors to combat cancer cells, while assessing the feasibility for its repurposing in the clinical setting.

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“…The GNPs anticancer activity is owed to their cytotoxic effects, inhibition of thiol-containing enzymes, particularly TrxR [ 23 ], damaging DNA [ 24 ] and mitochondrial functions [ 25 ]. Moreover, gold compounds can efficiently promote cellular mediated immune response against cancer through efficient antigen presentation on dendritic cells (DCs) [ 26 ]. Interestingly, there are other recognized antimicrobial and anticancer immune-regulatory effects of gold compounds that have been reviewed [ 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Gold Nanoparticles by Using Green Machinery: Characterization and In Vitro Toxicity

et al. 2021

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Green synthesis of gold nanoparticles (GNPs) with plant extracts has gained considerable interest in the field of biomedicine. Recently, the bioreduction nature of herbal extracts has helped to synthesize spherical GNPs of different potential from gold salt. In this study, a fast ecofriendly method was adopted for the synthesis of GNPs using fresh peel (aqueous) extracts of Benincasa hispida, which acted as reducing and stabilizing agents. The biosynthesized GNPs were characterized by UV–VIS and Fourier transform infrared spectroscopy, transmission electron microscopy (TEM), and dynamic light scattering. In addition, the in vitro antibacterial and anticancer activities of synthesized GNPs were investigated. The formation of gold nanoparticles was confirmed by the existence of a sharp absorption peak at 520 nm, corresponding to the surface plasmon resonance (SPR) band of the GNPs. TEM analysis revealed that the prepared GNPs were spherical in shape and had an average particle size of 22.18 ± 2 nm. Most importantly, the synthesized GNPs exhibited considerable antibacterial activity against different Gram-positive and Gram-negative bacteria. Furthermore, the biosynthesized GNPs exerted remarkable in vitro cytotoxicity against human cervical cancer cell line, while sparing normal human primary osteoblast cells. Such cytotoxic effect was attributed to the increased production of reactive oxygen species (ROS) that contributed to the damage of HeLa cells. Collectively, peel extracts of B. hispida can be efficiently used for the synthesis of GNPs, which can be adopted as a natural source of antimicrobial and anticancer agent.

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Recent Advances of Gold Compounds in Anticancer Immunity

Cited by 56 publications

References 114 publications

Auranofin-Mediated NRF2 Induction Attenuates Interleukin 1 Beta Expression in Alveolar Macrophages

Auranofin-Mediated NRF2 Induction Attenuates Interleukin 1 Beta Expression in Alveolar Macrophages

The gold complex auranofin: new perspectives for cancer therapy

Synthesis of Gold Nanoparticles by Using Green Machinery: Characterization and In Vitro Toxicity

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