Nanoparticles as Tools to Target Redox Homeostasis in Cancer Cells

Ciccarese, Francesco; Raimondi, Vittoria; Sharova, Evgeniya; Silic-Benussi, Micol; Ciminale, Vincenzo

doi:10.3390/antiox9030211

Cited by 44 publications

(21 citation statements)

References 69 publications

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“…The ever-increasing success of these therapies is due to their ability to induce the death of prokaryotic and eukaryotic cells through key cellular mechanisms such as that of induction of NP-mediated reactive oxygen species (ROS) generation [ 22 ]. Some NPs, once released into the body through different internalization methods such as oral, parenteral, inhalation administration and skin adsorption, can affect redox homeostasis both by generating ROS or lessening scavenging pathways [ 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

Biomedical Applications of Reactive Oxygen Species Generation by Metal Nanoparticles

et al. 2020

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The design, synthesis and characterization of new nanomaterials represents one of the most dynamic and transversal aspects of nanotechnology applications in the biomedical field. New synthetic and engineering improvements allow the design of a wide range of biocompatible nanostructured materials (NSMs) and nanoparticles (NPs) which, with or without additional chemical and/or biomolecular surface modifications, are more frequently employed in applications for successful diagnostic, drug delivery and therapeutic procedures. Metal-based nanoparticles (MNPs) including metal NPs, metal oxide NPs, quantum dots (QDs) and magnetic NPs, thanks to their physical and chemical properties have gained much traction for their functional use in biomedicine. In this review it is highlighted how the generation of reactive oxygen species (ROS), which in many respects could be considered a negative aspect of the interaction of MNPs with biological matter, may be a surprising nanotechnology weapon. From the exchange of knowledge between branches such as materials science, nanotechnology, engineering, biochemistry and medicine, researchers and clinicians are setting and standardizing treatments by tuning ROS production to induce cancer or microbial cell death.

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Section: Introductionmentioning

confidence: 99%

Biomedical Applications of Reactive Oxygen Species Generation by Metal Nanoparticles

et al. 2020

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“…Several recent studies suggested that NPs induce cytotoxicity through ROS generation and oxidative damage of cellular constituents [ 9 , 10 , 11 ]. Recent research also indicated that generation of intracellular ROS levels in a controlled way can be exploited as a therapeutic tool for cancer treatment [ 12 , 13 ]. In this regard, relatively higher levels of ROS observed in cancer cells as compared to their normal counterparts represent a promising tool to target cancer cell selectively [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Barium Titanate (BaTiO3) Nanoparticles Exert Cytotoxicity through Oxidative Stress in Human Lung Carcinoma (A549) Cells

et al. 2020

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Barium titanate (BaTiO3) nanoparticles (BT NPs) have shown exceptional characteristics such as high dielectric constant and suitable ferro-, piezo-, and pyro-electric properties. Thus, BT NPs have shown potential to be applied in various fields including electro-optical devices and biomedicine. However, very limited knowledge is available on the interaction of BT NPs with human cells. This work was planned to study the interaction of BT NPs with human lung carcinoma (A549) cells. Results showed that BT NPs decreased cell viability in a dose- and time-dependent manner. Depletion of mitochondrial membrane potential and induction of caspase-3 and -9 enzyme activity were also observed following BT NP exposure. BT NPs further induced oxidative stress indicated by induction of pro-oxidants (reactive oxygen species and hydrogen peroxide) and reduction of antioxidants (glutathione and several antioxidant enzymes). Moreover, BT NP-induced cytotoxicity and oxidative stress were effectively abrogated by N-acetyl-cysteine (an ROS scavenger), suggesting that BT NP-induced cytotoxicity was mediated through oxidative stress. Intriguingly, the underlying mechanism of cytotoxicity of BT NPs was similar to the mode of action of ZnO NPs. At the end, we found that BT NPs did not affect the non-cancerous human lung fibroblasts (IMR-90). Altogether, BT NPs selectively induced cytotoxicity in A549 cells via oxidative stress. This work warrants further research on selective cytotoxicity mechanisms of BT NPs in different types of cancer cells and their normal counterparts.

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“…An imbalance of redox homeostasis can result in numerous diseases, including cancer ( Ju et al, 2017 ; Liu et al, 2019 ). A sustained increase in the production of ROS has been detected in most cancers, promoting both tumorigenesis and tumor progression ( Waris and Ahsan, 2006 ; Liou and Storz, 2010 ; Ciccarese et al, 2020 ). However, tumor cells also can detoxify from ROS by upregulating the expression levels of antioxidant enzymes, indicating that disturbance of a delicate balance in intracellular ROS levels contributes to cancer cell function ( Liou and Storz, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

Caffeine Targets G6PDH to Disrupt Redox Homeostasis and Inhibit Renal Cell Carcinoma Proliferation

Liu

et al. 2020

Front. Cell Dev. Biol.

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Glucose-6-phosphate dehydrogenase (G6PDH) is the rate-limiting enzyme in the pentose phosphate pathway (PPP) and plays a crucial role in the maintenance of redox homeostasis by producing nicotinamide adenine dinucleotide phosphate (NADPH), the major intracellular reductant. G6PDH has been shown to be a biomarker and potential therapeutic target for renal cell carcinoma (RCC). Here, we report a previously unknown biochemical mechanism through which caffeine, a well-known natural small molecule, regulates G6PDH activity to disrupt cellular redox homeostasis and suppress RCC development and progression. We found that caffeine can inhibit G6PDH enzymatic activity. Mechanistically, caffeine directly binds to G6PDH with high affinity ( K D = 0.1923 μM) and competes with the coenzyme NADP + for G6PDH binding, as demonstrated by the decreased binding affinities of G6PDH for its coenzyme and substrate. Molecular docking studies revealed that caffeine binds to G6PDH at the structural NADP + binding site, and chemical cross-linking analysis demonstrated that caffeine inhibits the formation of dimeric G6PDH. G6PDH inhibition abrogated the inhibitory effects of caffeine on RCC cell growth. Moreover, inhibition of G6PDH activity by caffeine led to a reduction in the intracellular levels of NADPH and reactive oxygen species (ROS), and altered the expression of redox-related proteins in RCC cells. Accordingly, caffeine could inhibit tumor growth through inhibition of G6PDH activity in vivo . Taken together, these results demonstrated that caffeine can target G6PDH to disrupt redox homeostasis and inhibit RCC tumor growth, and has potential as a therapeutic agent for the treatment of RCC.

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Nanoparticles as Tools to Target Redox Homeostasis in Cancer Cells

Cited by 44 publications

References 69 publications

Biomedical Applications of Reactive Oxygen Species Generation by Metal Nanoparticles

Biomedical Applications of Reactive Oxygen Species Generation by Metal Nanoparticles

Barium Titanate (BaTiO3) Nanoparticles Exert Cytotoxicity through Oxidative Stress in Human Lung Carcinoma (A549) Cells

Caffeine Targets G6PDH to Disrupt Redox Homeostasis and Inhibit Renal Cell Carcinoma Proliferation

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