Unfolding New Roles for Guanine-Based Purines and Their Metabolizing Enzymes in Cancer and Aging Disorders

Iorio, Patrizia Di; Beggiato, Sarah; Ronci, Maurizio; Nedel, Cláudia Beatriz; Tasca, Carla I.; Zuccarini, Mariachiara

doi:10.3389/fphar.2021.653549

Cited by 9 publications

(13 citation statements)

References 73 publications

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“…Among the noble-metal nanoparticles, spherical cuprous oxide nanoparticles (β-Cu 2 O NPs) of the cuprite phase are most widely used in diverse biological applications, but recently they are used in carcinoma therapy effectively with the best results among its functions as an immunomodulator in cellular immunity like vitamin B 12 (cyanocobalamin) . Carcinoma cells remain insensitive to antiproliferative signals and apoptosis . Transition metals have gained attention for their promising anticancer activity as these play a significant role to reduce the adverse effects, drug resistance, and higher efficacy for cancer treatment.…”

Section: Introductionmentioning

confidence: 99%

“…49 Carcinoma cells remain insensitive to antiproliferative signals and apoptosis. 50 Transition metals have gained attention for their promising anticancer activity as these play a significant role to reduce the adverse effects, drug resistance, and higher efficacy for cancer treatment. Among these metals, cuprous oxide nanoparticles (β-Cu 2 O NPs) of the cuprite phase show anticancer activity because of their variable oxidation states as well as kinetic and physiological stability.…”

Section: Introductionmentioning

confidence: 99%

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One-Pot Surface Modification of β-Cu₂O NPs for Biocatalytic Performance against A-549 Lung Carcinoma Cell Lines through Docking Analysis

et al. 2021

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The physicochemical approaches and biological principles in bio-nanotechnology favor specially functionalized nanosized particles. Cuprous oxide nanoparticles (β-Cu2O NPs) of cuprite phase with a little tenorite (CuO) may be very effective in the development of novel therapeutic approaches against several fatalities including A-549 lung carcinoma cell lines. Consequently, the synthesis of β-Cu2O NPs for the improvement in the therapeutic index and drug delivery application is becoming an effective strategy in conventional anticarcinoma treatment. Hence, surface-enhanced nanosized spherical cuprous oxide nanoparticles (β-Cu2O NPs) of cuprite phase were successfully prepared using poly(ethylene glycol) (PEG) as an amphiphilic nonionic surfactant and l-ascorbic acid (K3[Cu(Cl5)]@LAA-PEG) reduced to cuprites β-Cu2O NPs via the sonochemical route. Less improved toxicity and better solubility of β-Cu2O NPs compared with Axitinib were a major reason for producing β-Cu2O NPs from K3[Cu(Cl5)]@LAA-PEG (LAA, l-ascorbic acid, PEG, poly(ethylene glycol) (PEG)). These nanoparticle syntheses have been suggested to influence their cytotoxicity, free-radical scavenging analysis, and reactive oxygen species (ROS) using poly(ethylene glycol) (PEG) and l-ascorbic acid (LAA) as coated and grafted materials due to their dose-dependent nature and IC50 calculations. The surface morphology of the formed β-Cu2O NPs has been examined via UV–vis spectroscopy, Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy with energy diffraction scattering spectroscopy (SEM@EDS), field emission scanning electron microscopy (FESEM), and transmission electron microscopy (TEM) analysis. X-ray diffraction (XRD) and Brunauer–Emmett–Teller (BET) surface analysis results confirm the presence of pure cuprite with a very little amount of tenorite (CuO) phase, Dynamic light scattering (DLS) confirms the negative ζ-value with stable nature. Docking was performed using PDB of lung carcinomas and others, as rigid receptors, whereas the β-Cu2O NP cluster was treated as a flexible ligand.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

One-Pot Surface Modification of β-Cu₂O NPs for Biocatalytic Performance against A-549 Lung Carcinoma Cell Lines through Docking Analysis

et al. 2021

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“…Guanosine (GUO) belongs to the family of the guanine-based purines (GBPs), which comprises other pharmacologically active molecules such as guanosine triphosphate and monophosphate (GTP and GMP, respectively), and the GUO metabolite, guanine (GUA). Numerous studies have shown that GBPs are neuroprotective agents contributing to nervous tissue repair upon brain injury (reviewed in [ 105 , 152 , 153 ]). GUO, in particular, exhibits anticonvulsant, antiparkinsonian, anxiolytic and antidepressant effects [ 152 , 153 ].…”

Section: Influence Of the Purinergic Signaling On The Main Functions ...mentioning

confidence: 99%

Bidirectional Control between Cholesterol Shuttle and Purine Signal at the Central Nervous System

Passarella

Ronci

Liberto

et al. 2022

IJMS

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Recent studies have highlighted the mechanisms controlling the formation of cerebral cholesterol, which is synthesized in situ primarily by astrocytes, where it is loaded onto apolipoproteins and delivered to neurons and oligodendrocytes through interactions with specific lipoprotein receptors. The “cholesterol shuttle” is influenced by numerous proteins or carbohydrates, which mainly modulate the lipoprotein receptor activity, function and signaling. These molecules, provided with enzymatic/proteolytic activity leading to the formation of peptide fragments of different sizes and specific sequences, could be also responsible for machinery malfunctions, which are associated with neurological, neurodegenerative and neurodevelopmental disorders. In this context, we have pointed out that purines, ancestral molecules acting as signal molecules and neuromodulators at the central nervous system, can influence the homeostatic machinery of the cerebral cholesterol turnover and vice versa. Evidence gathered so far indicates that purine receptors, mainly the subtypes P2Y2, P2X7 and A2A, are involved in the pathogenesis of neurodegenerative diseases, such as Alzheimer’s and Niemann–Pick C diseases, by controlling the brain cholesterol homeostasis; in addition, alterations in cholesterol turnover can hinder the purine receptor function. Although the precise mechanisms of these interactions are currently poorly understood, the results here collected on cholesterol–purine reciprocal control could hopefully promote further research.

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“…A significant number of studies reported that the dysregulation of cGMP/PKG signaling pathway accounts for numerous pathologies, including vascular and ventricular dysfunction, fibrosis, neurodegenerative disorders, hypertrophy and cancer [ 16 , 17 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

“…A cyclic GMP/PKG signaling cascade can be triggered among other causes, by NO, a multi-faceted compound eliciting often opposite biological effects in different organ systems [ 18 , 20 , 21 ]. NO is an inorganic free radical gas synthesized via the oxidation of L-arginine by nitric oxide synthase (NOS), which exists in three isoforms, Ca 2+ /calmodulin-dependent neuronal NOS (nNOS or NOS1) and endothelial NOS (eNOS or NOS3), and Ca 2+ /calmodulin-independent inducible NOS (iNOS-NOS2) [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Pros and Cons of Pharmacological Manipulation of cGMP-PDEs in the Prevention and Treatment of Breast Cancer

Iorio

Ronci

Giuliani

et al. 2021

IJMS

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The cyclic nucleotides, cAMP and cGMP, are ubiquitous second messengers responsible for translating extracellular signals to intracellular biological responses in both normal and tumor cells. When these signals are aberrant or missing, cells may undergo neoplastic transformation or become resistant to chemotherapy. cGMP-hydrolyzing phosphodiesterases (PDEs) are attracting tremendous interest as drug targets for many diseases, including cancer, where they regulate cell growth, apoptosis and sensitization to radio- and chemotherapy. In breast cancer, PDE5 inhibition is associated with increased intracellular cGMP levels, which is responsible for the phosphorylation of PKG and other downstream molecules involved in cell proliferation or apoptosis. In this review, we provide an overview of the most relevant studies regarding the controversial role of PDE inhibitors as off-label adjuvants in cancer therapy.

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Unfolding New Roles for Guanine-Based Purines and Their Metabolizing Enzymes in Cancer and Aging Disorders

Cited by 9 publications

References 73 publications

One-Pot Surface Modification of β-Cu₂O NPs for Biocatalytic Performance against A-549 Lung Carcinoma Cell Lines through Docking Analysis

One-Pot Surface Modification of β-Cu₂O NPs for Biocatalytic Performance against A-549 Lung Carcinoma Cell Lines through Docking Analysis

Bidirectional Control between Cholesterol Shuttle and Purine Signal at the Central Nervous System

Pros and Cons of Pharmacological Manipulation of cGMP-PDEs in the Prevention and Treatment of Breast Cancer

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Unfolding New Roles for Guanine-Based Purines and Their Metabolizing Enzymes in Cancer and Aging Disorders

Cited by 9 publications

References 73 publications

One-Pot Surface Modification of β-Cu2O NPs for Biocatalytic Performance against A-549 Lung Carcinoma Cell Lines through Docking Analysis

One-Pot Surface Modification of β-Cu2O NPs for Biocatalytic Performance against A-549 Lung Carcinoma Cell Lines through Docking Analysis

Bidirectional Control between Cholesterol Shuttle and Purine Signal at the Central Nervous System

Pros and Cons of Pharmacological Manipulation of cGMP-PDEs in the Prevention and Treatment of Breast Cancer

Contact Info

Product

Resources

About

One-Pot Surface Modification of β-Cu₂O NPs for Biocatalytic Performance against A-549 Lung Carcinoma Cell Lines through Docking Analysis

One-Pot Surface Modification of β-Cu₂O NPs for Biocatalytic Performance against A-549 Lung Carcinoma Cell Lines through Docking Analysis