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Metals and Cancer

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 30 April 2024 | Viewed by 7464

Special Issue Editors

Dr. Emil Malucelli

E-Mail Website
Guest Editor
Department of Pharmacy and Biotechnology, University of Bologna, 40127 Bologna, Italy
Interests: X-ray synchrotron-based techniques; biomineralization; osteoblastic differentiation; 3D cell culture; cellular imaging
Special Issues, Collections and Topics in MDPI journals
Dr. Concettina Cappadone

E-Mail Website
Guest Editor
Department of Pharmacy and Biotechnology, University of Bologna, 40127 Bologna, Italy
Interests: cancer; magnesium; MDR; cell cycle; bone; differentiation
Special Issues, Collections and Topics in MDPI journals
Dr. Alessandra Gianoncelli

E-Mail Website
Guest Editor
ELETTRA Sincrotrone Trieste S.C.p.A., 34149 Trieste, Italy
Interests: X-ray microscopy; X-ray fluorescence; ptychography and related applications in life sciences; environmental science and cultural heritage
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Metals are fundamental cellular elements for a number of biological processes, including the fundamental metabolic pathways such as energy transduction and cell proliferation. Several metals, such as Ca2+, K+, Na+, Mg2+, Zn2+, and Fe2+/Fe3+, are essential for mitochondrial function and cellular metabolism, including oxidative phosphorylation, mitochondrial integrity, proliferative signal transduction, and apoptosis. As a consequence, alterations in metal levels and/or changes in the expression of proteins involved in metal metabolism have been documented in different pathologies and several types of cancers.

Moreover, considering the key role of metals for cell growth, the development of drugs capable of metal sequestration has become an attractive target for the development of novel anti-cancer agents.

Furthermore, a large body of preclinical and clinical studies on dietary deficiencies indicates that metal dis-regulation triggers neoplastic cell transformation and/or reduces the anti-tumor functions of immune cells by controlling a plethora of chemical and biological reactions.

This Special Issue aims to encourage innovation and research activities in this field.

We invite researchers to contribute original research and review articles regarding the involvement of metal level and metabolism in cancer occurrence, progression, and prognosis.

Dr. Emil Malucelli
Dr. Concettina Cappadone
Dr. Alessandra Gianoncelli
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cancer
  • metal
  • cell metabolism
  • mitochondria
  • cell proliferation

Published Papers (6 papers)

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Research

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16 pages, 3269 KiB  
Article
Assessment of the Electrolyte Heterogeneity of Tissues in Mandibular Bone-Infiltrating Head and Neck Cancer Using Laser-Induced Breakdown Spectroscopy
by Philipp Winnand, Klaus Olaf Boernsen, Mark Ooms, Marius Heitzer, Nils Vohl, Matthias Lammert, Frank Hölzle and Ali Modabber
Int. J. Mol. Sci. 2024, 25(5), 2607; https://doi.org/10.3390/ijms25052607 - 23 Feb 2024
Viewed by 753
Abstract
Laser-induced breakdown spectroscopy (LIBS) was recently introduced as a rapid bone analysis technique in bone-infiltrating head and neck cancers. Research efforts on laser surgery systems with controlled tissue feedback are currently limited to animal specimens and the use of nontumorous tissues. Accordingly, this [...] Read more.
Laser-induced breakdown spectroscopy (LIBS) was recently introduced as a rapid bone analysis technique in bone-infiltrating head and neck cancers. Research efforts on laser surgery systems with controlled tissue feedback are currently limited to animal specimens and the use of nontumorous tissues. Accordingly, this study aimed to characterize the electrolyte composition of tissues in human mandibular bone-infiltrating head and neck cancer. Mandible cross-sections from 12 patients with bone-invasive head and neck cancers were natively investigated with LIBS. Representative LIBS spectra (n = 3049) of the inferior alveolar nerve, fibrosis, tumor stroma, and cell-rich tumor areas were acquired and histologically validated. Tissue-specific differences in the LIBS spectra were determined by receiver operating characteristics analysis and visualized by principal component analysis. The electrolyte emission values of calcium (Ca) and potassium (K) significantly (p < 0.0001) differed in fibrosis, nerve tissue, tumor stroma, and cell-rich tumor areas. Based on the intracellular detection of Ca and K, LIBS ensures the discrimination between the inferior alveolar nerve and cell-rich tumor tissue with a sensitivity of ≥95.2% and a specificity of ≥87.2%. The heterogeneity of electrolyte emission values within tumorous and nontumorous tissue areas enables LIBS-based tissue recognition in mandibular bone-infiltrating head and neck cancer. Full article
(This article belongs to the Special Issue Metals and Cancer)
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14 pages, 2031 KiB  
Article
Quantitative MRI Evaluation of Ferritin Overexpression in Non-Small-Cell Lung Cancer
by Mekhla Singhania, Amira Zaher, Casey F. Pulliam, Khaliunaa Bayanbold, Charles C. Searby, Joshua D. Schoenfeld, Kranti A. Mapuskar, Melissa A. Fath, Bryan G. Allen, Douglas R. Spitz and Michael S. Petronek
Int. J. Mol. Sci. 2024, 25(4), 2398; https://doi.org/10.3390/ijms25042398 - 18 Feb 2024
Viewed by 906
Abstract
Cancer cells frequently present elevated intracellular iron levels, which are thought to facilitate an enhanced proliferative capacity. Targeting iron metabolism within cancer cells presents an avenue to enhance therapeutic responses, necessitating the use of non-invasive models to modulate iron manipulation to predict responses. [...] Read more.
Cancer cells frequently present elevated intracellular iron levels, which are thought to facilitate an enhanced proliferative capacity. Targeting iron metabolism within cancer cells presents an avenue to enhance therapeutic responses, necessitating the use of non-invasive models to modulate iron manipulation to predict responses. Moreover, the ubiquitous nature of iron necessitates the development of unique, non-invasive markers of metabolic disruptions to develop more personalized approaches and enhance the clinical utility of these approaches. Ferritin, an iron storage enzyme that is often upregulated as a response to iron accumulation, plays a central role in iron metabolism and has been frequently associated with unfavorable clinical outcomes in cancer. Herein, we demonstrate the successful utility, validation, and functionality of a doxycycline-inducible ferritin heavy chain (FtH) overexpression model in H1299T non-small-cell lung cancer (NSCLC) cells. Treatment with doxycycline increased the protein expression of FtH with a corresponding decrease in labile iron in vitro and in vivo, as determined by calcein-AM staining and EPR, respectively. Moreover, a subsequent increase in TfR expression was observed. Furthermore, T2* MR mapping effectively detected FtH expression in our in vivo model. These results demonstrate that T2* relaxation times can be used to monitor changes in FtH expression in tumors with bidirectional correlations depending on the model system. Overall, this study describes the development of an FtH overexpression NSCLC model and its correlation with T2* mapping for potential use in patients to interrogate iron metabolic alterations and predict clinical outcomes. Full article
(This article belongs to the Special Issue Metals and Cancer)
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14 pages, 3493 KiB  
Article
Metallomic Signatures of Lung Cancer and Chronic Obstructive Pulmonary Disease
by Belén Callejón-Leblic, Saida Sánchez Espirilla, Carolina Gotera-Rivera, Rafael Santana, Isabel Díaz-Olivares, José M. Marín, Ciro Casanova Macario, Borja García Cosio, Antonia Fuster, Ingrid Solanes García, Juan P. de-Torres, Nuria Feu Collado, Carlos Cabrera Lopez, Carlos Amado Diago, Amparo Romero Plaza, Luis Alejandro Padrón Fraysse, Eduardo Márquez Martín, Margarita Marín Royo, Eva Balcells Vilarnau, Antonia Llunell Casanovas, Cristina Martínez González, Juan Bautista Galdíz Iturri, Celia Lacárcel Bautista, José Luis Gómez-Ariza, Antonio Pereira-Vega, Luis Seijo, José Luis López-Campos, Germán Peces-Barba and Tamara García-Barreraadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2023, 24(18), 14250; https://doi.org/10.3390/ijms241814250 - 18 Sep 2023
Cited by 1 | Viewed by 1081
Abstract
Lung cancer (LC) is the leading cause of cancer deaths, and chronic obstructive pulmonary disease (COPD) can increase LC risk. Metallomics may provide insights into both of these tobacco-related diseases and their shared etiology. We conducted an observational study of 191 human serum [...] Read more.
Lung cancer (LC) is the leading cause of cancer deaths, and chronic obstructive pulmonary disease (COPD) can increase LC risk. Metallomics may provide insights into both of these tobacco-related diseases and their shared etiology. We conducted an observational study of 191 human serum samples, including those of healthy controls, LC patients, COPD patients, and patients with both COPD and LC. We found 18 elements (V, Al, As, Mn, Co, Cu, Zn, Cd, Se, W, Mo, Sb, Pb, Tl, Cr, Mg, Ni, and U) in these samples. In addition, we evaluated the elemental profiles of COPD cases of varying severity. The ratios and associations between the elements were also studied as possible signatures of the diseases. COPD severity and LC have a significant impact on the elemental composition of human serum. The severity of COPD was found to reduce the serum concentrations of As, Cd, and Tl and increased the serum concentrations of Mn and Sb compared with healthy control samples, while LC was found to increase Al, As, Mn, and Pb concentrations. This study provides new insights into the effects of LC and COPD on the human serum elemental profile that will pave the way for the potential use of elements as biomarkers for diagnosis and prognosis. It also sheds light on the potential link between the two diseases, i.e., the evolution of COPD to LC. Full article
(This article belongs to the Special Issue Metals and Cancer)
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21 pages, 4173 KiB  
Article
New Copper Complexes with Antibacterial and Cytotoxic Activity
by Adriana Corina Hangan, Roxana Liana Lucaciu, Alexandru Turza, Lucia Dican, Bogdan Sevastre, Emöke Páll, Luminița Simona Oprean and Gheorghe Borodi
Int. J. Mol. Sci. 2023, 24(18), 13819; https://doi.org/10.3390/ijms241813819 - 07 Sep 2023
Cited by 3 | Viewed by 1280
Abstract
The discovery of a new non-toxic metal complex with biological activity represents a very active area of research. Two Cu+2 complexes, [Cu4(L1)4(OH)4(DMF)2(H2O)] (C1) (HL1 = N-(5-ethyl-[1,3,4]–thiadiazole–2-yl)-benzenesulfonamide) and [Cu(L2)2(phen)(H2O)] [...] Read more.
The discovery of a new non-toxic metal complex with biological activity represents a very active area of research. Two Cu+2 complexes, [Cu4(L1)4(OH)4(DMF)2(H2O)] (C1) (HL1 = N-(5-ethyl-[1,3,4]–thiadiazole–2-yl)-benzenesulfonamide) and [Cu(L2)2(phen)(H2O)] (C2) (HL2 = N-(5-(4-methylphenyl)-[1,3,4]–thiadiazole–2-yl)-naphtalenesulfonamide), with two new ligands were synthesized. The X-ray crystal structures of the complexes were determined. In both complexes, Cu+2 is five-coordinated, forming a CuN2O3 and CuN4O chromophore, respectively. The ligands act as monodentate, coordinating the metal ion through a single Nthiadiazole atom; for the two complexes, the molecules from the reaction medium (phenantroline, dimethylformamide and water) are also involved in the coordination of Cu+2. The complexes have a distorted square pyramidal square-planar geometry. The compounds were characterized by FT-IR and UV-Vis spectroscopy. Using the microdilution method, the antibacterial activity of the complexes was determined against four Gram-positive and two Gram-negative bacteria, with Gentamicin as the positive control. Cytotoxicity studies were carried out on two tumor cell lines (HeLa, DLD-1) and on a normal cell line (HFL1) using the MTT method and Cisplatin as a positive control. Flow cytometric assessment of apoptosis induced by the complexes on the three cell lines was also performed. Both complexes present in vitro biological activities but complex C2 is more active. Full article
(This article belongs to the Special Issue Metals and Cancer)
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Review

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19 pages, 1327 KiB  
Review
Toxicological Aspects Associated with Consumption from Electronic Nicotine Delivery System (ENDS): Focus on Heavy Metals Exposure and Cancer Risk
by Silvia Granata, Fabio Vivarelli, Camilla Morosini, Donatella Canistro, Moreno Paolini and Lucy C. Fairclough
Int. J. Mol. Sci. 2024, 25(5), 2737; https://doi.org/10.3390/ijms25052737 - 27 Feb 2024
Viewed by 979
Abstract
Tobacco smoking remains one of the leading causes of premature death worldwide. Electronic Nicotine Delivery Systems (ENDSs) are proposed as a tool for smoking cessation. In the last few years, a growing number of different types of ENDSs were launched onto the market. [...] Read more.
Tobacco smoking remains one of the leading causes of premature death worldwide. Electronic Nicotine Delivery Systems (ENDSs) are proposed as a tool for smoking cessation. In the last few years, a growing number of different types of ENDSs were launched onto the market. Despite the manufacturing differences, ENDSs can be classified as “liquid e-cigarettes” (e-cigs) equipped with an atomizer that vaporizes a liquid composed of vegetable glycerin (VG), polypropylene glycol (PG), and nicotine, with the possible addition of flavorings; otherwise, the “heated tobacco products” (HTPs) heat tobacco sticks through contact with an electronic heating metal element. The presence of some metals in the heating systems, as well as in solder joints, involves the possibility that heavy metal ions can move from these components to the liquid, or they can be adsorbed into the tobacco stick from the heating blade in the case of HTPs. Recent evidence has indicated the presence of heavy metals in the refill liquids and in the mainstream such as arsenic (As), cadmium (Cd), chromium (Cr), nickel (Ni), copper (Cu), and lead (Pb). The present review discusses the toxicological aspects associated with the exposition of heavy metals by consumption from ENDSs, focusing on metal carcinogenesis risk. Full article
(This article belongs to the Special Issue Metals and Cancer)
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26 pages, 2924 KiB  
Review
Cancer 3D Models for Metallodrug Preclinical Testing
by Diogo M. Engrácia, Catarina I. G. Pinto and Filipa Mendes
Int. J. Mol. Sci. 2023, 24(15), 11915; https://doi.org/10.3390/ijms241511915 - 25 Jul 2023
Viewed by 1587
Abstract
Despite being standard tools in research, the application of cellular and animal models in drug development is hindered by several limitations, such as limited translational significance, animal ethics, and inter-species physiological differences. In this regard, 3D cellular models can be presented as a [...] Read more.
Despite being standard tools in research, the application of cellular and animal models in drug development is hindered by several limitations, such as limited translational significance, animal ethics, and inter-species physiological differences. In this regard, 3D cellular models can be presented as a step forward in biomedical research, allowing for mimicking tissue complexity more accurately than traditional 2D models, while also contributing to reducing the use of animal models. In cancer research, 3D models have the potential to replicate the tumor microenvironment, which is a key modulator of cancer cell behavior and drug response. These features make cancer 3D models prime tools for the preclinical study of anti-tumoral drugs, especially considering that there is still a need to develop effective anti-cancer drugs with high selectivity, minimal toxicity, and reduced side effects. Metallodrugs, especially transition-metal-based complexes, have been extensively studied for their therapeutic potential in cancer therapy due to their distinctive properties; however, despite the benefits of 3D models, their application in metallodrug testing is currently limited. Thus, this article reviews some of the most common types of 3D models in cancer research, as well as the application of 3D models in metallodrug preclinical studies. Full article
(This article belongs to the Special Issue Metals and Cancer)
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