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Cancers
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The Role of Nitric Oxide in Cancer Treatment
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The Role of Nitric Oxide in Cancer Treatment

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (31 October 2021) | Viewed by 9322

Special Issue Editor

Prof. Catherine Paul

E-Mail Website
Guest Editor
Laboratory of Immunology and Immunotherapy of Cancers, EPHE, PSL Research University, Paris, France. Laboratory of Immunology and Immunotherapy of Cancers (LIIC), EA7269, University of Burgundy Franche-Comté, Dijon, France
Interests: cancer; immunology; immunotherapy; nitric oxide; cancer treatment; imaging biomarkers; chemotherapy combinations

Special Issue Information

Dear Colleagues,

Nitric oxide (NO) is an endogenous and ubiquitous signaling molecule that not only plays a critical role in physiological processes, but also in pathological situations such as cancer. NO has been described as having a dual, pro-, and antitumor role in cancer, depending on its concentration in the microenvironment, the nature of NO derivatives, and the NO-induced post-translational modifications. Progress in understanding the role of NO in cancer biology has generated significant advances in the use of NO donor-based therapies.

This Special Issue entitled “The Role of Nitric Oxide in Cancer Treatment” aims at highlighting original research that deals with the role of NO in cancer development, with a specific focus on different strategies to increase NO availability in the tumor microenvironment.  

Prof. Catherine Paul
Guest Editor

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 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. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). 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 therapy
  • nitric oxide
  • S-nitrosylation
  • therapy combination
  • tumor microenvironment modulators

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Published Papers (3 papers)

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Research

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17 pages, 2371 KiB  
Article
The Nitric Oxide Donor [Zn(PipNONO)Cl] Exhibits Antitumor Activity through Inhibition of Epithelial and Endothelial Mesenchymal Transitions
by Valerio Ciccone, Arianna Filippelli, Chiara Bacchella, Enrico Monzani and Lucia Morbidelli
Cancers 2022, 14(17), 4240; https://doi.org/10.3390/cancers14174240 - 31 Aug 2022
Cited by 6 | Viewed by 2317
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue The Role of Nitric Oxide in Cancer Treatment)
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17 pages, 3362 KiB  
Article
NCX-4040, a Unique Nitric Oxide Donor, Induces Reversal of Drug-Resistance in Both ABCB1- and ABCG2-Expressing Multidrug Human Cancer Cells
by Birandra K. Sinha, Lalith Perera and Ronald E. Cannon
Cancers 2021, 13(7), 1680; https://doi.org/10.3390/cancers13071680 - 2 Apr 2021
Cited by 13 | Viewed by 2821
Abstract
The emergence of multidrug resistance (MDR) in the clinic is a significant problem for a successful treatment of human cancers. Overexpression of various ABC transporters (P-gp, BCRP and MRP’s), which remove anticancer drugs in an ATP-dependent manner, is linked to the emergence of [...] Read more.
The emergence of multidrug resistance (MDR) in the clinic is a significant problem for a successful treatment of human cancers. Overexpression of various ABC transporters (P-gp, BCRP and MRP’s), which remove anticancer drugs in an ATP-dependent manner, is linked to the emergence of MDR. Attempts to modulate MDR have not been very successful in the clinic. Furthermore, no single agent has been found to significantly inhibit their functions to overcome clinical drug resistance. We have previously shown that nitric oxide (●NO) inhibits ATPase functions of ABC transporters, causing reversal of resistance to clinically active anticancer drugs. In this study, we have used cytotoxicity and molecular docking studies to show that NCX4040, a nitric oxide donor related to aspirin, inhibited the functions of ATPase which resulted in significant reversal of resistance to both adriamycin and topotecan in P-gp- and BCRP-expressing human cancer cell lines, respectively. We also used several other cytotoxic nitric oxide donors, e.g., molsidomine and S-nitroso glutathione; however, both P-gp- and BCRP-expressing cells were found to be highly resistant to these NO-donors. Molecular docking studies showed that NCX4040 binds to the nucleotide binding domains of the ATPase and interferes with further binding of ATP, resulting in decreased activities of these transporters. Our results are extremely promising and suggest that nitric oxide and other reactive species delivered to drug resistant tumor cells by well-designed nitric oxide donors could be useful in sensitizing anticancer drugs in multidrug resistant tumors expressing various ABC transporters. Full article
(This article belongs to the Special Issue The Role of Nitric Oxide in Cancer Treatment)
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Review

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22 pages, 2552 KiB  
Review
Glycyrrhizin as a Nitric Oxide Regulator in Cancer Chemotherapy
by Minsu Kim, Seok Chan Park and Dong Yun Lee
Cancers 2021, 13(22), 5762; https://doi.org/10.3390/cancers13225762 - 17 Nov 2021
Cited by 10 | Viewed by 3342
Abstract
Chemotherapy is used widely for cancer treatment; however, the evolution of multidrug resistance (MDR) in many patients limits the therapeutic benefits of chemotherapy. It is important to overcome MDR for enhanced chemotherapy. ATP-dependent efflux of drugs out of cells is the main mechanism [...] Read more.
Chemotherapy is used widely for cancer treatment; however, the evolution of multidrug resistance (MDR) in many patients limits the therapeutic benefits of chemotherapy. It is important to overcome MDR for enhanced chemotherapy. ATP-dependent efflux of drugs out of cells is the main mechanism of MDR. Recent studies have suggested that nitric oxide (NO) can be used to overcome MDR by inhibiting the ATPase function of ATP-dependent pumps. Several attempts have been made to deliver NO to the tumor microenvironment (TME), however there are limitations in delivery. Glycyrrhizin (GL), an active compound of licorice, has been reported to both reduce the MDR effect by inhibiting ATP-dependent pumps and function as a regulator of NO production in the TME. In this review, we describe the potential role of GL as an NO regulator and MDR inhibitor that efficiently reduces the MDR effect in cancer chemotherapy. Full article
(This article belongs to the Special Issue The Role of Nitric Oxide in Cancer Treatment)
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