Nitric oxide favours tumour-promoting inflammation through mitochondria-dependent and -independent actions on macrophages

Drehmer, Daiana; Luiz, João; Hernandez, Cesar Augusto Speck; Alves‐Filho, José C.; Hussell, Tracy; Townsend, Paul A.; Moncada, Salvador

doi:10.1016/j.redox.2022.102350

Cited by 14 publications

(10 citation statements)

References 79 publications

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“…Nitric oxide (NO) production was positively correlated with the intensity of the inflammatory response. 36 Therefore, the degree of inflammation in each group can be known from the NO concentration in the supernatant of each group. The results showed that Pt@ZIF-8@La could reduce the inflammatory response induced by Ti particles, and the anti-inflammatory ability was concentration-dependent (Figure S-8).…”

Section: Resultsmentioning

confidence: 99%

“…First, Ti particles (0.1 mg/mL) were cocultured with RAW 264.7 cells to induce inflammation, and then different concentrations of Pt@ZIF-8@La were added for treatment. Nitric oxide (NO) production was positively correlated with the intensity of the inflammatory response . Therefore, the degree of inflammation in each group can be known from the NO concentration in the supernatant of each group.…”

Section: Resultsmentioning

confidence: 99%

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Bimetallic Metal–Organic Framework for Mitigating Aseptic Osteolysis

Pan

Miao

Deng

et al. 2023

ACS Appl. Mater. Interfaces

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The disability rate of joint diseases can be reduced by the use of artificial joints, but joint loosening at a late state limits the lifespan and surgical efficacy of the joints. Wear particles can be recognized by macrophages and induce cells to produce reactive oxygen species (ROS) and inflammatory factors, causing persistent inflammation and decreased osteogenic activity, which ultimately leads to loosening of joint prostheses. Here, the platinum (Pt) nanozymes with excellent ROS scavenging and anti-inflammatory capabilities were encapsulated in zinc imidazolium zeolite framework-8 (ZIF-8), and then the osteogenic active element lanthanum (La) was introduced through ion exchange to finally construct a bimetallic metal−organic framework (Pt@ZIF-8@ La). In vitro and in vivo experiments demonstrated that this multifunctional nanoplatform possessed the functions of efficient scavenging of ROS, immune regulation, and promotion of osteogenic differentiation. Meanwhile, the mechanism is explored that Pt@ZIF-8@La can also promote osteogenic mineralization by upregulating the ratio of the osteoprotegerin (OPG)/receptor activator of the NF-κB ligand (RANKL), which can achieve a synergistic therapeutic effect of immunomodulation and osteogenesis, thereby realizing the purpose of relieving aseptic osteolysis.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Bimetallic Metal–Organic Framework for Mitigating Aseptic Osteolysis

Pan

Miao

Deng

et al. 2023

ACS Appl. Mater. Interfaces

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“…Other factors that probably influence tumor responsiveness are the presence and quality of the inflammatory environment and the intrinsic ability to produce NO, represented mainly by iNOS whose levels can vary in time and within the tumor mass. We can hypothesize that when the levels of iNOS are high (as in squamous tumors, and colon and prostate cancer) [ 62 , 63 ], the best approach is to use NOS inhibitors, whereas NO-based derivatives can be proposed for tumors with low/moderate levels of iNOS, thereby promoting a reduction in NO levels and inflammation. Indeed, the cellular models used in the present study showed modest expression of iNOS.…”

Section: Discussionmentioning

confidence: 99%

“…While we demonstrated an anti-inflammatory effect (see the inhibition of TGF-β1 signaling and the physiological protective effect of NO in the cardiovascular system), NO has been demonstrated to play a crucial role in the development of chronic inflammation. As example, the presence of NO in cancer may regulate tumor-associated macrophage metabolism and function, favoring the persistence of inflammation in tumorigenesis and cancer stemness [ 63 , 64 , 65 , 66 , 67 ]. These findings appear tissue-specific, since in most of the reports the association high NO levels with inflammation, oxidative status, DNA damage and tumorigenesis has been described for cancer of the gastrointestinal apparatus, upper airways, the reproductive organs and the breast.…”

Section: Discussionmentioning

confidence: 99%

The Nitric Oxide Donor [Zn(PipNONO)Cl] Exhibits Antitumor Activity through Inhibition of Epithelial and Endothelial Mesenchymal Transitions

Ciccone

Filippelli

Bacchella

et al. 2022

Cancers

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Exogenous nitric oxide appears a promising therapeutic approach to control cancer progression. Previously, a nickel-based nonoate, [Ni(SalPipNONO)], inhibited lung cancer cells, along with impairment of angiogenesis. The Zn(II) containing derivatives [Zn(PipNONO)Cl] exhibited a protective effect on vascular endothelium. Here, we have evaluated the antitumor properties of [Zn(PipNONO)Cl] in human lung cancer (A549) and melanoma (A375) cells. Metastasis initiates with the epithelial–mesenchymal transition (EMT) process, consisting of the acquisition of invasive and migratory properties by tumor cells. At not cytotoxic levels, the nonoate significantly impaired A549 and A375 EMT induced by transforming growth factor-β1 (TGF-β1). Reduction of the mesenchymal marker vimentin, upregulated by TGF-β1, and restoration of the epithelial marker E-cadherin, reduced by TGF-β1, were detected in both tumor cell lines in the presence of Zn-nonoate. Further, the endothelial–mesenchymal transition achieved in a tumor-endothelial cell co-culture was assessed. Endothelial cells co-cultured with A549 or A375 acquired a mesenchymal phenotype with increased vimentin, alpha smooth muscle actin and Smad2/3, and reduced VE-cadherin. The presence of [Zn(PipNONO)Cl] maintained a typical endothelial phenotype. In conclusion, [Zn(PipNONO)Cl] appears a promising therapeutic tool to control tumor growth and metastasis, by acting on both tumor and endothelial cells, reprogramming the cells toward their physiologic phenotypes.

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“…Besides, the produced NO could also improve the efficacy of starvation therapy in turn. peroxynitrite anions, 32,33 inflammation enhancement, 34,35 and P53 upregulation and cytochrome release. 36,37 Generally, these series of antitumor effects of NO were collectively called NO therapy.…”

Section: Introductionmentioning

confidence: 99%

Glutathione/Glucose-Depleting Nanoparticles with NO Generation for Ferroptosis/Starvation/NO-Induced Cancer Therapy

Fan

Chen

et al. 2023

Chem. Mater.

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Depleting intracellular glutathione (GSH) has emerged as a potent strategy to combat cancer. However, the existing GSH-depleting agents are too toxic or ineffective and standalone GSH depletion fails to yield a satisfactory curative effect. Herein, we present an intelligent nanoparticle that possesses GSH depletion, glucose consumption accompanied with H2O2 production, and NO generation properties for multimodal cancer therapy. The nanoparticle is constructed by synthesis of tetrasulfide bond-doped mesoporous silica nanoparticles followed by conjugating glucose oxidase (GOx) on the surface and loading l-arginine (l-Arg) into the mesopores. In this nanoparticle, the doped tetrasulfide bonds can quickly deplete GSH, which increases the cellular reactive oxygen species concentration to induce ferroptosis and meanwhile triggers particle biodegradation to expose the loaded l-Arg. Moreover, the elevated H2O2 level activates l-Arg to release NO for NO therapy. GOx consumes glucose to initiate starvation therapy and simultaneously produces a large amount of H2O2. Importantly, the produced H2O2 can not only potentiate ferroptosis but also promote NO release to enhance NO therapy. Besides, NO could in turn improve the efficacy of starvation therapy by damaging the mitochondria to block energy supply. In vitro and in vivo studies demonstrate that the nanoparticles show a great synergistic effect of ferroptosis/starvation/NO therapy, which can significantly kill cancer cells and remarkably inhibit tumor growth without obvious side effects. Therefore, we think that the designed nanoparticles may provide a promising paradigm for synergistic cancer therapy and hold a prospect in clinical trials.

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Nitric oxide favours tumour-promoting inflammation through mitochondria-dependent and -independent actions on macrophages

Cited by 14 publications

References 79 publications

Bimetallic Metal–Organic Framework for Mitigating Aseptic Osteolysis

Bimetallic Metal–Organic Framework for Mitigating Aseptic Osteolysis

The Nitric Oxide Donor [Zn(PipNONO)Cl] Exhibits Antitumor Activity through Inhibition of Epithelial and Endothelial Mesenchymal Transitions

Glutathione/Glucose-Depleting Nanoparticles with NO Generation for Ferroptosis/Starvation/NO-Induced Cancer Therapy

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