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Biomolecules
Special Issues
Cisplatin in Diseases: Molecular Mechanisms of Action
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Cisplatin in Diseases: Molecular Mechanisms of Action

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: closed (31 July 2022) | Viewed by 14328

Special Issue Editors

Dr. Iva Potočnjak

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Guest Editor
Department of Medical Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine, University of Rijeka, Rijeka, Croatia
Interests: cisplatin; kidney injury; oxidative stress; autophagy; apoptosis; cancer; MAPK; phytochemicals
Prof. Dr. Georgi Momekov

E-Mail Website
Guest Editor
Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, 100 Sofia, Bulgaria
Interests: experimental anticancer chemotherapy; anticancer drug design; antineoplastic metallodrugs; antimicrobials; ethnopharmacology; phytopharmacology; targeted drug delivery systems; drug discovery; medicinal chemistry; pharmacokinetics; natural product chemistry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cisplatin is one of the most effective anticancer agents. It has been used for the last 50 years, and is still the treatment of choice for various solid cancers. Although cisplatin has been a research topic for many scientists all around the world, the exact mechanism of its action remains unclear. It has been shown that it exerts its activity through activation of various signaling pathways that can result in the induction of oxidative stress, inflammation, apoptosis, autophagy, and other processes. Despite its effectiveness in the treatment of malignancies, cisplatin exerts various toxicities: ototoxicity, nephrotoxicity, myelosuppression, nephrotoxicity, gastrointestinal and other toxicities that are limiting factors in its clinical use. Unfortunately, the mechanisms of cisplatin toxicities have not been completely elucidated, and no agents have been identified that can protect from all toxicities without interfering with its chemotherapeutic effects. The struggle remains to find agents that can mitigate those side effects, because molecular mechanisms in those toxicities and related injuries remain unclear. Although different types of agents can partly prevent toxicities caused by cisplatin, they are not yet approved during cisplatin chemotherapy because of their unknown effects on interference with therapy due to their insufficiently explored mechanisms of action. Cisplatin has a future, as it continues to be a prescribed chemotherapy. Clarifying its molecular mechanisms of action in diseases is a good strategy to overcome challenges associated with attenuating its side effects and increasing its efficacy. There is still hope that in the near future we will be able to precisely target different research axes and clarify new molecular mechanisms implicated in diseases, identify new biomarkers to predict cisplatin-associated toxicities, and develop new formulations in clinical trials, therefore overcoming the major problem of treatment failures.

Dr. Iva Potočnjak
Prof. Dr. Georgi Momekov
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. Biomolecules is an international peer-reviewed open access monthly 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 2700 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

  • cisplatin
  • chemotherapeutic
  • cancer
  • side effects
  • ototoxicity
  • nephrotoxicity
  • myelosuppression
  • nephrotoxicity
  • gastrointestinal toxicity
  • combination therapy

Published Papers (4 papers)

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Review

12 pages, 1156 KiB  
Review
Cisplatin Resistance: Genetic and Epigenetic Factors Involved
by Yuliannis Lugones, Pía Loren and Luis A. Salazar
Biomolecules 2022, 12(10), 1365; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12101365 - 24 Sep 2022
Cited by 21 | Viewed by 4066
Abstract
Cisplatin (CDDP) is the drug of choice against different types of cancer. However, tumor cells can acquire resistance to the damage caused by cisplatin, generating genetic and epigenetic changes that lead to the generation of resistance and the activation of intrinsic resistance mechanisms [...] Read more.
Cisplatin (CDDP) is the drug of choice against different types of cancer. However, tumor cells can acquire resistance to the damage caused by cisplatin, generating genetic and epigenetic changes that lead to the generation of resistance and the activation of intrinsic resistance mechanisms in cancer cells. Among them, we can find mutations, alternative splicing, epigenetic-driven expression changes, and even post-translational modifications of proteins. However, the molecular mechanisms by which CDDP resistance develops are not clear but are believed to be multi-factorial. This article highlights a description of cisplatin, which includes action mechanism, resistance, and epigenetic factors involved in cisplatin resistance. Full article
(This article belongs to the Special Issue Cisplatin in Diseases: Molecular Mechanisms of Action)
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15 pages, 1538 KiB  
Review
MicroRNAs Involved in Intrinsic Apoptotic Pathway during Cisplatin-Induced Nephrotoxicity: Potential Use of Natural Products against DDP-Induced Apoptosis
by Pía Loren, Yuliannis Lugones, Nicolás Saavedra, Kathleen Saavedra, Isis Páez, Nelia Rodriguez, Patricia Moriel and Luis A. Salazar
Biomolecules 2022, 12(9), 1206; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12091206 - 31 Aug 2022
Cited by 1 | Viewed by 2025
Abstract
Cisplatin (cis-diamminedichloroplatinum (II), DDP) is an antineoplastic agent widely used in the treatment of solid tumors because of its extensive cytotoxic activity. However, the main limiting side effect of DDP use is nephrotoxicity, a rapid deterioration in kidney function due to [...] Read more.
Cisplatin (cis-diamminedichloroplatinum (II), DDP) is an antineoplastic agent widely used in the treatment of solid tumors because of its extensive cytotoxic activity. However, the main limiting side effect of DDP use is nephrotoxicity, a rapid deterioration in kidney function due to toxic chemicals. Several studies have shown that epigenetic processes are involved in DDP-induced nephrotoxicity. Noncoding RNAs (ncRNAs), a class of epigenetic processes, are molecules that regulate gene expression under physiological and pathological conditions. MicroRNAs (miRNAs) are the most characterized class of ncRNAs and are engaged in many cellular processes. In this review, we describe how different miRNAs regulate some pathways leading to cell death by apoptosis, specifically the intrinsic apoptosis pathway. Accordingly, many classes of natural products have been tested for their ability to prevent DDP-induced apoptosis. The study of epigenetic regulation for underlying cell death is still being studied, which will allow new strategies for the diagnosis and therapy of this unwanted disease, which is presented as a side effect of antineoplastic treatment. Full article
(This article belongs to the Special Issue Cisplatin in Diseases: Molecular Mechanisms of Action)
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17 pages, 1427 KiB  
Review
Cisplatin-Induced Kidney Toxicity: Potential Roles of Major NAD+-Dependent Enzymes and Plant-Derived Natural Products
by Amany Iskander and Liang-Jun Yan
Biomolecules 2022, 12(8), 1078; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12081078 - 05 Aug 2022
Cited by 5 | Viewed by 3004
Abstract
Cisplatin is an FDA approved anti-cancer drug that is widely used for the treatment of a variety of solid tumors. However, the severe adverse effects of cisplatin, particularly kidney toxicity, restrict its clinical and medication applications. The major mechanisms of cisplatin-induced renal toxicity [...] Read more.
Cisplatin is an FDA approved anti-cancer drug that is widely used for the treatment of a variety of solid tumors. However, the severe adverse effects of cisplatin, particularly kidney toxicity, restrict its clinical and medication applications. The major mechanisms of cisplatin-induced renal toxicity involve oxidative stress, inflammation, and renal fibrosis, which are covered in this short review. In particular, we review the underlying mechanisms of cisplatin kidney injury in the context of NAD+-dependent redox enzymes including mitochondrial complex I, NAD kinase, CD38, sirtuins, poly-ADP ribosylase polymerase, and nicotinamide nucleotide transhydrogenase (NNT) and their potential contributing roles in the amelioration of cisplatin-induced kidney injury conferred by natural products derived from plants. We also cover general procedures used to create animal models of cisplatin-induced kidney injury involving mice and rats. We highlight the fact that more studies will be needed to dissect the role of each NAD+-dependent redox enzyme and its involvement in modulating cisplatin-induced kidney injury, in conjunction with intensive research in NAD+ redox biology and the protective effects of natural products against cisplatin-induced kidney injury. Full article
(This article belongs to the Special Issue Cisplatin in Diseases: Molecular Mechanisms of Action)
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22 pages, 767 KiB  
Review
Is Autophagy Always a Barrier to Cisplatin Therapy?
by Jingwen Xu and David A. Gewirtz
Biomolecules 2022, 12(3), 463; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12030463 - 17 Mar 2022
Cited by 23 | Viewed by 4292
Abstract
Cisplatin has long been a first-line chemotherapeutic agent in the treatment of cancer, largely for solid tumors. During the course of the past two decades, autophagy has been identified in response to cancer treatments and almost uniformly detected in studies involving cisplatin. There [...] Read more.
Cisplatin has long been a first-line chemotherapeutic agent in the treatment of cancer, largely for solid tumors. During the course of the past two decades, autophagy has been identified in response to cancer treatments and almost uniformly detected in studies involving cisplatin. There has been increasing recognition of autophagy as a critical factor affecting tumor cell death and tumor chemoresistance. In this review and commentary, we introduce four mechanisms of resistance to cisplatin followed by a discussion of the factors that affect the role of autophagy in cisplatin-sensitive and resistant cells and explore the two-sided outcomes that occur when autophagy inhibitors are combined with cisplatin. Our goal is to analyze the potential for the combinatorial use of cisplatin and autophagy inhibitors in the clinic. Full article
(This article belongs to the Special Issue Cisplatin in Diseases: Molecular Mechanisms of Action)
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